BACKGROUND. This study examined the analgesiceffect of local ketamine infiltration, compared with placebo and systemic ketamine, in a human model of inflammatory pain. METHODS: Inflammatory pain was induced by a burn (at 47 degrees C for 7 min; wound size, 2.5 x 5 cm) on the calf in 15 volunteers on 3 separate days with 7-day intervals. They received either (1) subcutaneous infiltration with ketamine in the burn area (local treatment) and contralateral placebo injections, or (2) subcutaneous ketamine contralateral to the burn (systemic treatment) and placebo in the burn area, or (3) placebo on both sides. The study was double-blinded and the order of the treatments was randomized. Hyperalgesia to mechanical and heat stimuli was examined by von Frey hairs and contact thermodes (3.75 and 12.5 cm2), and pain was rated using a visual analog scale (0-100). RESULTS: The burns produced significant hyperalgesia. Local ketamine infiltration reduced pain during the burn injury compared with systemic treatment and placebo (P < 0.01). Heat pain thresholds were increased by local ketamine treatment compared with placebo immediately after injection (P < 0.03), and so were the mechanical pain thresholds (P = 0.02). Secondary hyperalgesia and suprathreshold pain responses to heat and mechanical stimuli were not significantly affected by local ketamine. No difference between local ketamine and placebo could be detected 1 h and 2 h after the burn. CONCLUSIONS: Ketamine infiltration had brief local analgesiceffects, but several measures of pain and hyperalgesia were unaffected. Therefore, a clinically relevant effect of peripheral ketamine in acute pain seems unlikely.

Ketamine, in subanesthetic doses, produces systemic analgesia in chronic pain settings, an action largely attributed to block of N-methyl-D-aspartate receptors in the spinal cord and inhibition of central sensitization processes. N-methyl-D-aspartate receptors also are located peripherally on sensory afferent nerve endings, and this provided the initial impetus for exploring peripheral applications of ketamine. Ketamine also produces several other pharmacological actions (block of ion channels and receptors, modulation of transporters, anti-inflammatory effects), and while these may require higher concentrations, after topical (e.g., as gels, creams) and peripheral application (e.g., localized injections), local tissue concentrations are higher than those after systemic administration and can engage lower affinity mechanisms. Peripheral administration of ketamine by localized injection produced some alterations in sensory thresholds in experimental trials in volunteers and in complex regional pain syndrome subjects in experimental settings, but many variables were unaltered. There are several case reports of analgesia after topical application of ketamine given alone in neuropathic pain, but controlled trials have not confirmed such effects. A combination of topical ketamine with several other agents produced pain relief in case, and case series, reports with response rates of 40% to 75% in retrospective analyses. In controlled trials of neuropathic pain with topical ketamine combinations, there were improvements in some outcomes, but optimal dosing and drug combinations were not clear. Given orally (as a gargle, throat swab, localized peritonsillar injections), ketamine produced significant oral/throat analgesia in controlled trials in postoperative settings. Topical analgesics are likely more effective in particular conditions (patient factors, disease factors), and future trials of topical ketamine should include a consideration of factors that could predispose to favorable outcomes. PMID:24945127

Full Text Available Laurinda Lemos1,2, Ramalho Fontes3, Sara Flores2, Pedro Oliveira4, Armando Almeida11Life and Health Sciences Research Institute (ICVS, School of Health Sciences, Campus de Gualtar, University of Minho, Braga, Portugal; 2Hospital Center of Alto Ave, Unit of Fafe, Fafe, Portugal; 3Department of Neurology, Hospital São Marcos, Braga, Portugal; 4Products and Systems Engineering, Campus de Azurém, University of Minho, Guimarães, PortugalAbstract: Treatment of trigeminal neuralgia (TN is achieved by using adjuvant analgesics like antiepileptics, with carbamazepine (CBZ being the first-line approach for TN patients, although side effects may be present. Other approaches using gabapentin, namely when associated with peripheralanalgesic block of TN trigger points with the local anesthetic ropivacaine (ROP, resulted in decreased pain and daily drug intake (reduced side effects. This study evaluates if the association between CBZ and the peripheral block with ROP reinforces the clinical value of CBZ. In this parallel, double-blinded study, idiopathic TN patients were randomized to receive during 4 weeks either CBZ (CBZ; n = 21 or CBZ associated with the peripheralanalgesic block using ROP (CBZ + ROP; n = 24. The primary outcome measures were the following: i pain intensity, evaluated by the numerical rating scale; ii number of pain crises; and iii number needed to treat. Evaluation points were at the beginning (day 1 and end (day 29 of treatment and after a follow-up of 5 months (month 6. Both protocols resulted in a decrease of pain intensity and number of pain crises, but only the association CBZ + ROP showed i a significant stronger reduction in pain intensity at month 6 and ii a significant decrease in the daily dose of CBZ given to patients (both at day 29 and month 6. In contrast, the daily dose in CBZ-only patients remained constant or even increased. The number needed to treat for the association CBZ + ROP over the CBZ protocol reduced from 5 at the end of the 4-week treatment to 3 after the 5-month follow-up. Data reinforce the use of CBZ as a primary tool to control pain in TN patients, as the association CBZ + ROP i improves the clinical qualities of CBZ, ii strongly reduces the daily dose of CBZ, and iii reduces the potential side effects attributed to high doses of CBZ.Keywords: trigeminal neuralgia, carbamazepine, ropivacaine, therapeutical association, pain intensity, daily dose

Despite immense advances in the treatment strategies, management of neuropathic pain remains unsatisfactory. Piracetam is a prototype of nootropic drugs, used to improve cognitive impairment. The present study was designed to investigate the effect of piracetam on peripheral neuropathic pain in rats. Neuropathic pain was induced by the chronic constriction injury of the sciatic nerve. Following this, piracetam was intraperitoneally administered for 2 weeks in doses of 50, 100 and 200 mg/kg, and pain was assessed by employing the behavioural tests for thermal hyperalgesia (hot plate and tail flick tests) and cold allodynia (acetone test). After the induction of neuropathic pain, significant development of thermal hyperalgesia and cold allodynia was observed. The administration of piracetam (50 mg/kg) did not have any significant effect on all the behavioural tests. Further, piracetam (100 mg/kg) also had no effect on the hot plate and tail flick tests; however it significantly decreased the paw withdrawal duration in the acetone test. Piracetam in a dose of 200 mg/kg significantly modulated neuropathic pain as observed from the increased hot plate and tail flick latencies, and decreased paw withdrawal duration (in acetone test). Therefore, the present study suggests the potential use of piracetam in the treatment of neuropathic pain, which merits further clinical investigation. PMID:24831122

Dipyrone (metamizole) is an analgesic pro-drug used to control moderate pain. It is metabolized in two major bioactive metabolites: 4-methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA). The aim of this study was to investigate the participation of peripheral CB1 and CB2 cannabinoid receptors activation in the anti-hyperalgesic effect of dipyrone, 4-MAA or 4-AA. PGE2 (100ng/50µL/paw) was locally administered in the hindpaw of male Wistar rats, and the mechanical nociceptive threshold was quantified by electronic von Frey test, before and 3h after its injection. Dipyrone, 4-MAA or 4-AA was administered 30min before the von Frey test. The selective CB1 receptor antagonist AM251, CB2 receptor antagonist AM630, cGMP inhibitor ODQ or KATP channel blocker glibenclamide were administered 30min before dipyrone, 4-MAA or 4-AA. The antisense-ODN against CB1 receptor expression was intrathecally administered once a day during four consecutive days. PGE2-induced mechanical hyperalgesia was inhibited by dipyrone, 4-MAA, and 4-AA in a dose-response manner. AM251 or ODN anti-sense against neuronal CB1 receptor, but not AM630, reversed the anti-hyperalgesic effect mediated by 4-AA, but not by dipyrone or 4-MAA. On the other hand, the anti-hyperalgesic effect of dipyrone or 4-MAA was reversed by glibenclamide or ODQ. These results suggest that the activation of neuronal CB1, but not CB2 receptor, in peripheral tissue is involved in the anti-hyperalgesic effect of 4-aminoantipyrine. In addition, 4-methylaminoantipyrine mediates the anti-hyperalgesic effect by cGMP activation and KATP opening. PMID:25058903

Full Text Available Liliane J Dableh, James L HenryDepartment of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, CanadaAbstract: Chronic neuropathic pain that may arise from various nerve injuries or insults remains notoriously difficult to manage. The neuronal isoform of the enzyme nitric oxide synthase (nNOS has been shown to be involved in the spinal transmission of nociception in animal models of chronic pain. The aim of this study is to evaluate the effect of single dose and repeated administration of a selective nNOS inhibitor. Rats were unilaterally implanted with a 2-mm polyethylene cuff around the sciatic nerve. Paw withdrawal thresholds were measured using von Frey filament stimulation. Rats were given 10, 20, or 30 mg/kg of 7-nitroindazole (7-NI, or vehicle, on days 2, 5, and 7 after model induction, respectively. Paw withdrawal thresholds were measured before and at 30 and 60 min after injection. 7-NI significantly increased paw withdrawal thresholds at 60 min at the 20 and 30 mg/kg dosages. In the second part of this study, rats were given 20 mg/kg 7-NI daily for five days starting immediately after cuff implantation (days 0 to 4, and the cuff was removed on day 4. Withdrawal thresholds were measured intermittently over a 24-day observation period. No differences in withdrawal thresholds were observed between drug and vehicle-treated rats. Therefore, early and repeated administration of 7-NI did not affect the development or progression of the model. In conclusion, inhibition of nNOS had an analgesic but not a pre-emptive effect in this model of peripheral neuropathic pain.Keywords: neuronal nitric oxide synthase, nitric oxide, 7-nitroindazole, neuropathic pain, peripheral nerve injury, nociception

Full Text Available Mechanisms of endogenous pain control are significant. Increasing studies have clearly produced evidence for the clinical usefulness of opioids in peripheral analgesia. The immune system uses mechanisms of cell migration not only to fight pathogens but also to control pain and inflammation within injured tissue. It has been demonstrated that peripheral inflammatory pain can be effectively controlled by an interaction of immune cell-derived opioid peptides with opioid receptors on peripheral sensory nerve terminals. Experimental and clinical studies have clearly shown that activation of peripheral opioid receptors with exogenous opioid agonists and endogenous opioid peptides are able to produce significant analgesic and anti-inflammatory effects, without central opioid mediated side effects (e.g. respiratory depression, sedation, tolerance, dependence. This article will focus on the role of opioids in peripheral inflammatory conditions and the clinical implications of targeting peripheral opioid receptors.

The analgesic mechanism underlying the efficacy of topical diclofenac in the treatment of musculoskeletal pain is incompletely understood. The present study investigated whether intramuscular injection of diclofenac (0.1mg/ml, approximately 340microM) could attenuate jaw-closer muscle nociceptor discharge and mechanical sensitization induced by activation of peripheral 5-hydroxytryptamine (serotonin) or excitatory amino acid receptors in anesthetized Sprague-Dawley rats. Diclofenac inhibited nociceptor discharge evoked by NMDA, but had no effect on nociceptor discharge evoked by 5-hydroxytryptamine or AMPA. Subsequent experiments revealed that diclofenac-mediated inhibition of NMDA-evoked nociceptor discharge was competitive. Intramuscular injection of 5-hydroxytryptamine, NMDA and AMPA also decreased nociceptor mechanical threshold, however, only the mechanical sensitization produced by NMDA was reversed by diclofenac. Co-administration of the proinflammatory prostaglandin PGE(2) did not alter the ability ofdiclofenac to significantly attenuate NMDA-evoked nociceptor discharge or NMDA-induced mechanical sensitization. Intramuscular injection of either diclofenac or the competitive NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (50mM) alone could elevate nociceptor mechanical threshold for a 30min period post-injection. The present study indicates that in vivo, diclofenac can exert a selective, competitive inhibition of peripheral NMDA receptors at muscle concentrations achievable after topical administration of diclofenac containing preparations. This property may contribute to the analgesiceffect of topical diclofenac when used for muscle pain.

The hydroalcohol extracts of Achillea millefolium L. (AM) and Artemisia vulgaris L. (AV), both belonging to the Asteraceae family, were evaluated by the hot plate, writhing, formalin and intestinal transit tests in an attempt to confirm their folk use as analgesic, antiinflammatory and antispasmodic agents. AM 500 and 1000 mg/kg significantly inhibited abdominal contortions by 65% and 23%, respectively, whereas AV 500 and 1000 mg/kg inhibited them by 48% and 59%, respectively. None of the extracts produced differences in the intestinal transit in mice, nor in the response time in the hot plate or in the immediate or late responses in the formalin test. In HPLC/DAD analyses 'fingerprint', monitored at 360 and 270 nm, both hydroalcohol extracts showed the same flavonoid glycoside as a principal constituent, which was identified as rutin. A high content of caffeic acid derivatives were also found in both extracts. The main differences were observed at 240 nm: AM had a higher content of rutin, while in AV the hydroxybenzoic acid derivative was the major component. PMID:18844327

BACKGROUND AND OBJECTIVES: Glucocorticoids are well-known adjuvant analgesics in certain chronic pain states. There is, however, a paucity of data on their analgesic efficacy in acute pain. Therefore, the aim of the study was to examine the analgesiceffects of dexamethasone in a validated burn model of acute inflammatory pain in humans. METHODS: Twenty-two volunteers were investigated in a double-blind, randomized, placebo-controlled cross-over study. Intravenous dexamethasone 8 mg or placebo was administered on 2 separate study days. Two hours after drug administration, a first-degree burn injury was produced on the medial aspect of the nondominant calf (12.5 cm2, 47 degrees C for 7 minutes). Quantitative sensory testing included pain ratings to thermal and mechanical stimuli (visual analog scale [VAS]), assessments of thermal and mechanical detection thresholds, and areas of allodynia and secondary hyperalgesia. RESULTS: The burn injury induced significant increases in erythema (P .6). There were no significant differences between treatments in regard to skin erythema (P >.8), thermal or mechanical thresholds (P >.2), thermal or mechanical pain response (P >.2), or mechanical secondary hyperalgesia (P >.2). Dexamethasone had no analgesiceffects in normal skin. CONCLUSIONS: The study indicates that systemic administration of dexamethasone 2 hours before a burn injury does not reduce the inflammatory-mediated changes in quantitative sensory thresholds, pain perception, or skin erythema in humans.

Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesiceffects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesiceffects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

Full Text Available Introduction: Several researches have reported that stress is able to inhibit the development of morphine tolerance via activating of Hypothalamic-Pituitary-Adrenal (HPA axis. In the present study we tried to examine the effect of epinephrine, the product of adrenal medulla, on the development of morphine tolerance. Methods: Analgesic tolerance was induced by intrathecal (i.t. injection of morphine 15 ?g/kg, twice a day for 5 days. To study the effect of epinephrine on morphine tolerance, epinephrine (2, 5, 10 or 20 ?g/kg, i.t. was administrated 20 minutes before morphine injection. Analgesia was assessed using tail flick test. Results: In animals that received combined treatments of morphine and epinephrine in doses 2, 5, 10 or 20 ?g/ kg for 5 days, at 6th day, morphine produced a more potent analgesia comparing with animals that received saline and morphine during days 1-5. Following tolerance induction during first 5 days, co-administration of epinephrine and morphine during days 6 – 10 reduced the initial tolerance as it induced potent analgesia on day 11th. Conclusion: Our results showed that i.t. administration of epinephrine is able to inhibit and reverse the analgesic tolerance to morphine. It also suggests the possible role of adrenal medulla and epinephrine in mediating the inhibitory effect of stress and HPA activation of the development of analgesic tolerance to morphine.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that induces changes in excitability, and activation of brain neurons and neuronal circuits. It has been observed that beyond regional effects under the electrodes, tDCS also alters activity of remote interconnected cortical and subcortical areas. This makes the tDCS stimulation technique potentially promising for modulation of pain syndromes. Indeed, utilizing specific montages, tDCS resulted in analgesiceffects in experimental settings, as well as in post-operative acute pain and chronic pain syndromes. The promising evidence of tDCS-induced analgesiceffects raises the challenging and complex question of potential physiologic mechanisms that underlie/mediate the accomplished pain relief. Here we present hypotheses on how the specific montages and targets for stimulation may affect the pain processing network. PMID:24133434

Full Text Available Previous studies have suggested that ketamine, an N-methyl-D-aspartate (NMDA receptor antagonist, provides a pre-emptive analgesiceffect and pre-emptive analgesia improves postoperative pain management. The aim of this study was to determine the effict of pre-incisional vs. post-incisional intravenous low dose of racemic ketamine in postoperative pain in children undergoing inguinal hernia repair. Seventy-five children aged 1-6 years who were scheduled for inguinal herniorrhaphy were included in a prospective, double-blind randomized controlled trial. Patients were randomly allocated to three groups (pre-incisional, post-incisional and control. Patients in pre-incisional group received an intravenous bolus of racemic ketamine (0.25 mg/kg before surgical incision and patients in post-incisional group received the same dose of racemic ketamine after surgical incision. Children of control group received intravenous boluses of normal saline. In post anesthesia care unit and pediatric surgical ward, the degree of pain and sedation, additional analgesic requirements and side effects were evaluated. There were no differences between groups with respect to demographic and hemodynamic parameters. Pain and sedation scores were not statistically different between groups during 24 h study. In addition, there was no significant difference among groups in number of supplementary analgesic requirements and postoperative nausea and vomiting in the first 24 h. No other side effects were reported during the study period. We found that low dose racemic ketamine administered prior to surgical incision has no pre-emptive effect on post-operative pain and supplementary analgesic requirement during the first 24 h after herniorrhaphy in pediatric patients. "n

Previous studies have suggested that ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, provides a pre-emptive analgesiceffect and pre-emptive analgesia improves postoperative pain management. The aim of this study was to determine the effict of pre-incisional vs. post-incisional intravenous low dose of racemic ketamine in postoperative pain in children undergoing inguinal hernia repair. Seventy-five children aged 1-6 years who were scheduled for inguinal herniorrhaphy were includ...

Full Text Available Objective: To explore the hemostatic and analgesiceffect of Gonghuan Zhixue Tablet (GHZXT on mice and to produce experimental evidence for exploiting new drug for endometrorrhagia caused by Cu-intrauterine contraceptive device (Cu-IUD. Methods: Compared with 6-aminocaproic acid and notoginseng, the effects of GHZXT on clotting and bleeding time of mice with capillary method and severed tail were investigated; and compared with aspirin, the analgesiceffects of GHZXT on mice were investigated with hot plate and torsive body method. Results: The clotting time of mice was remarkably shortened with a rising of the dosage of GHZXT and the difference between each therapeutic group and distilled water group was remarkable. As compared with distilled water group, the bleeding time of each dosage group of GHZXT was obviously shortened; and each dosage of GHZXT could prolong the time of pain reaction to hot plate and decrease the degree of torsive body of the mice. Conclusion: Pharmacological experiment has proved that GHZXT has evident hemostatic and analgesic function.

Full Text Available In a randomized, double blind study , we compared post operative pain and analgesic requirement in patients undergoing cesarean section with two types of general anesthesia: standardized general anesthesia (control group=26 cases and preemptive low-dose ketamine (0.2 mg/kg administered prior to anesthesia induction (keratmine group=27 cases. Postoperative analgesia was provided for both groups using morphine intravenously based on visual analogue scale (VAS. After the operation we found that the time from the end of surgery to the first request for analgesic was longer in ketamine group (10.22±8 hrs than in the control group (1.65±1.01 hrs0 (P<0.001 Mean dose of morphine consumption over 24 hrs was less in the ketamine group (625±3.45 mg than in the control group (17.73±4.08 mg (P<0.001 VAS of pain scores were lower in ketamine group during 24 hr (P<0.001. APGAR Scores were similar between the groups. No patient in either group had postoperative hallucination. In conclusion, ketamine in low dose has a preemptive analgesia effect that reduces central sensitization in cesarean section and reduces postoperative analgesic requirement.

Full Text Available Objectives: To evaluate the preemptive effects of gabapentin on postoperative pain relief and its effect on meperidine consumption in patients undergoing tonsillectomy. Methods: This study took place in King Abdulaziz Naval Base Hospital in the year 2009. Sixty patients ASA I and II were randomly assigned in a prospective randomized double- blind placebo-control clinical trial. Gabapentine 1200 mg or placebo was given orally two hours before induction of anesthesia to patients undergoing tonsillectomy under general anesthesia. Postoperative pain score was recorded on a visual analogue scale at 1, 3, 6, 12, 18 and 24 postoperative hours. Patients received meperidine 1 mg/ kg i.m once every 4 h if pain score 3 or if requested by the patient. Total dose of meperidine consumption was recorded. Results: Thirty patients in the gabapentine group and 30 patients in the placebo group completed the study. Patients in gabapentine group had significantly lower pain score in comparison to placebo group. Total postoperative meperidine consumption in the gabapentin group was (48.8±33.9 VS 93.8 ± 54.6 in the placebo group (P< 0.001. There was higher incidence of nausea, vomiting, and use of antiemetic drugs in the placebo group. Conclusion: Preemptive use of gabapentine decreased pain score and post operative meperidine consumption and reduced meperidine ­related adverse effects in patients undergoing tonsillectomy under general anesthesia.

Oxycodone is a ?-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesiceffects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesiceffect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesiceffect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone. PMID:24618941

Oxycodone is a ?-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesiceffects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesiceffect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesiceffect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone. PMID:24618941

Full Text Available Objective: In this study, we aimed comparing early postoperative period analgesiceffectiveness and the effects on opioid consumption of intravenous dexketoprofen and lornoxicam that are given preemptively. Materials and Methods: Forty patients, planned elective mediastinoscopy, were included in this prospective randomized study. These patients were classified in two groups, group D for dexketoprofene trometamol and group L for lornoxicam, randomly. 20 minutes before the operation 50 mg dexketoprofene trometamol and 8 mg lornoxicam were injected intravenously for group D and group L respectively. In postoperative intensive care unit, pain scores, mean arterial pressures, heart rates and peripheric O2 saturations of patients were recorded at 0, 10, 20, 60, 90 and 120th minutes. Results: When we evaluate the VAS score of the groups, there was a significant decrease in group D in all measured timesstatistically compairing to group L (p0.05. Conclusion: Since intravenous dexketoprofen, applied preemptively, has more potent analgesiceffect and causing less opioid consumption in early postoperative period, is better than intravenous lornoxicam.

Full Text Available Purpose : Abutilon indicum (Linn. sweet (Malvaceae commonly called ?Country Mallow? is a perennial plant up to 3 m in height. It is abundantly found as a weed in the sub-Himalayan tract and in the hotter parts of India. The plant is traditionally used for treatment of several diseases like bronchitis, body ache, toothache, jaundice, diabetes, fever, piles, leprosy, ulcers, cystitis, gonorrhea, diarrhea, and so on. Abutilon indicum Linn. is reported to have hepatoprotective, hypoglycemic, antimicrobial, male contraceptive, and antidiarrheal activities. The present study was done to evaluate the analgesic potential of various extracts of the root of Abutilon indicum Linn. Materials and Methods : The powdered root (900 g was subjected to successive solvent extraction, with solvents in increasing order of polarity, namely, petroleum ether (60 - 80?C, methanol, and ethanol, using the soxhlet apparatus for 72 hours. The marc was extracted by cold maceration for 72 hours, to obtain a water-soluble extract. The peripheralanalgesic activity was studied using acetic acid-induced writhing method in Swiss albino mice (20 - 30 g, while the central analgesic activity was evaluated by the tail flick method and the tail immersion method. Results : Results indicated that all the tested extracts, except the methanol extract, exhibited significant analgesic activity in both animals? models. Petroleum ether extract showed higher analgesic activity. The activity may be related to the central mechanism or may be due to the peripheralanalgesic mechanisms. Conclusion : The present study authenticates the traditional use.

Full Text Available We examined preemptive analgesiceffect of caudal block in patients undergoing orthopaedic hip or lower extremities surgery.Forty children between ages of 1-12 years whom orthopaedics hip and or lower extremities surgery would be applied to were included into study. Fifteen minutes before surgical incision, in Group I, 0.125% bupivacaine 0.5 ml/kg was given for caudal anaesthesia. In Group II, caudal block was postoperatively applied with the same dose of drug. During postoperative period, patients were followed for 48 hours, and OPS “objective pain scale”, time to demand of first analgesic, and total analgesic consumption were recorded. In Group II, OPS score and total analgesic consumption were higher in initial 8 hours (P<0.05, P<0.001. Duration of first analgesic application was longer in Group I (P<0.001.We concluded that preoperative caudal block has preemptive analgesiceffect in children undergoing orthopaedic surgery.

Nimodipine, an L-type calcium channel blocker, can induce analgesia. However, it is not clear that this analgesiceffect is at the level of spinal or supraspinal pain pathway. In addition, it has been reported that the analgesiceffect of nifedipine, another L-type calcium channel blocker is related to the HPA axis, but there is no report indicating the role of this axis in the analgesiceffect of nimodipine. Methods: Analgesia was measured by tail-flick (TF) test involving spinal reflexes an...

Full Text Available Background. Gol-e-arvaneh with the scientific name of salvia hydrangea (Labiatea belongs to Salvia genus. In traditional medicine it has been used as analgesic, relieving headache, cold remedy, antipyretic and diuretic. Since until now this plant has not been investigated pharacologically. This study was aimed to find any anti-inflammatory or analgesic activity of the plant.
Methods. At first, total extract, flavonoid fraction and volatile oil was prepared. Analgesiceffect was assessed using light tail flick and acetic acid writhing test. Male wistar rats (180-220g and mice (25±2g were used in these tests. Carrageen in test was used for assessing anti-inflammatory activity.
Results. Total extract and flavonoid fraction could not produce analgesiceffect in light tail flick test, while morphine as a standard drug 15 and 30 min. after administration produced 35% and 90% of MPE respectively. In writhing test, total extract and flavonoid fraction had considerable analgesiceffect which was comparable to that of indomethacin. Results of Carageenin test showed that both total extract and flavonoid fraction had marked anti-inflammatory activity and volatile oil had only a slight effect.
Discussion. Since potent drugs (such as opioids show positive response to light tail flick test, it seems that the plant lacks such compounds. Considerable analgesic activity of total extract and flavonoid fraction in writhing test and also their anti-inflammatory activity indicate that this plant is probably useful for relieving pains, particularly with inflammatory origin.

Background and Objective: Due to the increased role of medicinal plants in therapy, the aim of this research was to study and compare the analgesiceffect of hydroalcoholic extract of the seeds of Vitis vinifera with morphine and aspirin as a common analgesic.Subjects and Methods: In this study, the hydroalcoholic extract of Vitis vinifera seed was prepared by maceration method. This study was done on male Wistar rat species. The animals were divided into 7 groups (n= 9): Negative control ...

Patients undergoing extractions of third molar teeth under general anesthesia were given a placebo, diclofenac (a nonsteroidal anti-inflammatory drug) 100 mg, or methadone (an opiate) 10 mg 60 to 90 min prior to surgery, and their pain scores and postoperative medication requirements were measured for 3 days. All patients received local anesthetic blocks and analgesic drugs during the perioperative period. There were no significant differences between the three groups in the pain scores and m...

Our objective was to study the anti-inflammatory and analgesic activity of extract of Spartium junceum L. flowers. Samples of flowers were collected from wild plants, dried, powdered, and extracted with hexane and methanol. The extracts were evaporated to dryness and then suspended in suitable solvent. They were then tested for anti-inflammatory activity in the carrageenin rat paw edema test and for analgesic activity in the Randall and Selitto mechanical pressure test and in the tail-flick test. Twenty-four hours after treatment, the gastric mucosa of each rat was observed macroscopically. Based on these results the hexane extract was fractioned by column chromatography, and the fractions obtained were tested in the same way. The results showed good anti-inflammatory activity only for a single fraction of the hexane extract, while all the extracts and all the other hexane fractions showed both peripheral and central analgesic activity. In rats treated with the tested compounds hyperemia and ulcers were absent. The data from this preliminary study reveal interesting pharmacological properties of S. junceum L. flowers extract related to the marked analgesic activity and the absence of gastric ulcerogenic activity. PMID:17004903

We studied the anti-inflammatory and analgesic activity of extracts of Sideritis syriaca L. herba. Samples were collected from the wild plant, dried, powdered, and extracted with hexane and methanol. The extracts were evaporated to dryness and then suspended in suitable solvent. They were then tested for anti-inflammatory activity in the carrageenin rat paw edema test and for analgesic activity in the Randall and Selitto test and in the tail-flick test. At 24 hours after the treatment, the gastric mucosa of each rat was observed macroscopically. Based on these results the hexane extract was fractionated by column chromatography, and the fractions were obtained tested in the same way. Results showed interesting anti-inflammatory activity only for the hexane extract and all the fractions obtained from it. All the extracts and all the other fractions showed both peripheral and central analgesic activity. In rats treated with the tested compounds hyperemia and ulcers were absent. The data from this preliminary study reveal interesting pharmacological properties of S. syriaca L. herba extracts related to the marked analgesic activity and the absence of gastric ulcerogenic activity. The same is for anti-inflammatory activity, but in this case it seems to be related only to the apolar fraction. PMID:16117615

Magnesium sulphate infusion decreases analgesic requirements after general anesthesia. Aim of this study was to assess the effects of postoperative magnesium infusion for 24 hours on duration of the block, sedation and postoperative analgesic consumption after brachial plexus block. After obtaining approval from local ethic committee, 70 ASA class I and II patients were included to the randomised double blind study. Brachial plexus block was performed using axillary approach with lignocaine 1.25% adrenaline 1/200 000 40 ml. Groups received 5 mg/kg bolus and 500 mg/h magnesium sulphate infusion or saline controls at the same volume during 24 hour. Analgesia and sedation were assessed while determining time to first pain and rescue analgesic, time to regain motor capability, visual analogue scale and sedation scores for every 4 hour during postoperative 24 h. period. While time to first pain and rescue analgesic was increased, total analgesic consumption was reduced significantly on magnesium infusion group (Meperidine: C: 36.3 +/- 42.6 mg, Mg: 11.7 +/- 12.2 mg, p: 0.001). Visual analogue scales were also observed to be lower in all periods. Time to motor block resolution, and sedation scores were similar. Magnesium sulphate infusion is thought as a safe and suitable adjunct for reducing analgesic consumption and possible complications without interfering daily activity in patients undergoing brachial plexus block. PMID:18095196

Full Text Available Analgesiceffect of aqueous and hydroalcoholic extracts of aeral parts of Hyptis suavolens, Nauclea latifolia and Ocimum gratissimum, three plants used in congolese folk medicine in pain, were tested on acetic acid and hot plate tests. All extracts manifest analgesiceffect on the two models used. The more active was the hydroalcoholic extract of Ocimum gratissimum which is not antagonized by naloxone and could potentiate analgesiceffect of paracetamol.

This prospective study assessed the postoperative analgesiceffect of intra-articular ketorolac, morphine, and bupivacaine during arthroscopic outpatient partial meniscectomy. Group 1 patients (n=20) received postoperative injection of 60 mg intra-articular ketorolac, group 2 patients (n=20) 10 cc intra-articular bupivacaine 0.25%, group 3 patients (n=20) 1 mg intra-articular morphine diluted in 10 cc saline, and group 4 patients (n=20, controls) only 10 cc saline. We evaluated the postoperative analgesiceffect (period measured from the end of the surgery until further analgesia was demanded), the level of postoperative pain (by visual analog scale 1, 2, 3, 12, and 24 h after surgery), and the need for additional pain medication (during the first 24 h after surgery). The best analgesiceffect was in patients treated with intra-articular ketorolac, and this was statistically significant in: postoperative analgesiceffect and the need for additional pain medication immediately after surgery, and after 24 h. No complications were found related to the intra-articular treatment. We conclude that 60 mg intra-articular ketorolac provides better analgesiceffect than 10 cc intra-articular bupivacaine 0.25% or 1 mg intra-articular morphine. PMID:15197428

Full Text Available Background/Aim. Ropivacaine is a relatively new longacting local anesthetic. The aim of this study was to compare the postoperative analgesiceffect of topical anesthetics ropivacaine 0.75% and lidocaine 2% with adrenaline in the postoperative treatment of periapical lesions in the maxilla. Methods. The study was conducted on 60 subjects, divided into two groups. The study-group received 0.75% ropivacaine without a vasoconstrictor, while the control group was treated with 2% lidocaine with adrenaline (1 : 80.000. Block anesthesia for n. infraorbitalis was used and local anesthetics were applied also on the palatine side for the end branches of n. nasopalatinus. The following parameters were observed: time elapsed from the application of an anesthetic until the first occurrence of pain after the surgery and first intake of an analgesic, the intensity of initial pain, pain intensity 6 h after the application of anesthetics and the total number of analgesics taken within 24 h after the completion of surgery. Results. The pain appeared statistically significantly earlier in the patients who had been given lidocaine with adrenaline (p < 0.001, while statistically significantly higher mean values of initial postoperative pain (p < 0.05 and pain intensity 6 h after the intervention (p < 0.01 were also registered in the same group of patients. In the period of 24 h upon the intervention, the study-group patients were taking less analgesics as compared to the control-group subjects (46.6% vs 73.3%, who were given analgesics earlier, although no statistically significant differences were observed related to the number of analgesic doses taken. Conclusion. The results of our study indicate a better postoperative analgesiceffect of ropivacaine as compared to lidocaine with adrenaline.

Full Text Available Previous studies have shown that the extract of Papaver rhoeas reduces morphine dependence, locomotor activity and reward. In present study, the effects of hydro-alcohol extract of Papaver Rhoeas on the tolerance to analgesiceffects of morphine in mice have been investigated using tail flick method. Subcutaneous (s.c. administration of morphine (1, 2, 5 and 10 mg/kg induced analgesia. However, intrapretoneal administration of the hydro-alcohol extract of Papaver rhoeas (25, 50 and 100 mg/kg had not an effects on analgesia. Reduction of analgesic in mice pretreated with morphine (50 mg/kg, twice daily; for 3 days, alone, indicated that tolerance has been developed. Hydro-alcohol extract of Papaver rhoeas (25, 50 and 100 mg/kg, i.p. administration, 30 min before each of three daily doses of morphine, attenuated the morphine tolerance dose-independently,indicating that administration of the extract reduces morphine tolerance in mice.

To compare the postoperative analgesiceffects of intra-articular levobupivacaine with bupivacaine following knee arthroscopy. Forty patients, aged between 20-60 years and undergoing elective knee arthroscopy were enrolled into the study protocol that was carried out in Tepecik Education and Research Hospital, Izmir, Turkey between January and June 2007. General anesthesia protocol was the same in all patients. At the end of surgery, the patients were randomly assigned into 2 groups (n=20 in each group). Group L received 20 ml 0.5% levobupivacaine and Group B received 20 ml 0.5% bupivacaine intra-articularly. We evaluated the level of postoperative pain (by visual analoque scale at 1, 2, 4, 6, 12, and 24 hours after surgery), first analgesic requirement time (period measured from the end of the surgery until further analgesia was demanded), and total analgesic consumption during 24 hours. There were no significant difference in the postoperative pain scores of the patients between groups. The first analgesic requirement times were not statistically different. Twelve patients in Group L (60%) and 9 patients in Group B (45%) needed no additional analgesic during the 24 hours (p>0.05). No complications and side effects were found related to the intra-articular treatment. The results of the study show that intra-articular 20 ml 0.5% levobupivacaine provides effective analgesia comparable to that provided by 20 ml 0.5% bupivacaine. (author) (author)

It has been observed that beyond regional effects under the electrodes, tDCS also alters activity of remote interconnected cortical and subcortical areas. This makes the tDCS stimulation technique potentially promising for modulation of pain syndromes. Indeed, utilizing specific montages, tDCS resulted in analgesiceffects in experimental settings, as well as in post-operative acute pain and chronic pain syndromes. The promising evidence of tDCS-induced analgesiceffects raises the challenging and complex question of potential physiologic mechanisms that underlie/mediate the accomplished pain relief. Here we present hypotheses on how the specific montages and targets for stimulation may affect the pain processing network.

Full Text Available Post-surgery pain is usually controlled by PRN drugs administered by nurses. According to the decision-making theories, this clinical decision-making depends on three factors: nurse-related factors; child-related factors; and hospital-related factors. This study deals with the first and second factors mentioned. This descriptive-analytic study aims at determining the perspective of nurses on factors which affect their decisions to administer the analgesic PRN to children after surgery in several chosen hospitals of Tehran. The study used a standardized questionnaire to collect data from 57 nurses in pediatric surgery wards. The questionnaire consisted of three parts: 1 nurses demographic data 2 20 clinical scenario for nurses to make a decision for prescribing either analgesic medication, non-analgesic medication or no medication where necessary and 3 12 factors which affect clinical decision-making in using analgesics.(in prioritizing among the above mentioned. The results show that factors such as age, nursing experience, pediatric nursing experience and motherhood were significantly related to choosing to use analgesics. Education and personal experience of extreme pain was also related to the type of analgesic chosen. Concerning the specifics of the children there was a significant difference between the choice to use analgesics and the type of analgesic used according to the various ages of the children. There was also a significant relationship between the type of surgery and the time of surgery and with the choice to use analgesics and the type of analgesics used, such that medication and analgesics were administered more frequently for complicated surgeries and in first 24 hours after surgery. Type of surgery, severity of pain, time of surgery and uneasy behaviors were selected respectively as the most effective in the administration of PRN analgesic drugs. Nurse and child related factors strongly influence nurses in making decisions to administer PRN analgesics postoperatively.

Full Text Available THE influence of circulating serotonin (5-HT on the effects of intra-articular administration of granisetron on temporomandibular joint (TMJ pain was investigated in 11 patients with chronic polyarthritides. An analgesiceffect superior to placebo has been shown previously.

Tolerance to the analgesiceffects of opioids has been demonstrated in laboratory animals after repeated drug administration, yet this effect has been studied less frequently under controlled laboratory conditions in humans. This within-subject, double-blind, placebo-controlled study was designed to determine if tolerance developed to the analgesic, subjective, and physiological effects of the commonly prescribed opioid oxycodone when it was administered daily for 5 days. The effects of oxycodone’s (0, 5, and 20 mg/70 kg, p.o.) were compared, using a within-session cumulative dosing procedure, on the 1st and 5th days of the ‘daily’ dosing phase to assess for tolerance; active oxycodone was administered on the 2nd-4th days of the daily dosing phase. Changes in the effects of oxycodone were also compared when the medication was only administered on the 1st and 5th day of a 5-day ‘intermittent’ dosing phase; placebo medication was administered on the 2nd–4th days of the intermittent dosing phase. A 9-day ‘washout’ period occurred between phases when no medication was administered. Healthy volunteers (N=10) with no history of drug dependence or current drug use participated in this outpatient study. Analgesia was assessed using the Cold-Pressor Test (CPT), pain and drug effects were measured using a variety of questionnaires, and pupil diameter was monitored as an index of physiological effects. When administered daily, no differences were observed in oxycodone-induced analgesia between the 1st and 5th days, but tolerance did develop to some of the positive subjective effects of oxycodone. In contrast, oxycodone-induced analgesia and participant ratings of some positive subjective drug effects were greater on the 5th day compared to the 1st day of the intermittent dosing phase. No differences in the miotic effects of oxycodone between the 1st and 5th days of either dosing phase were detected. Though obtained under limited experimental conditions, these findings suggest that tolerance may not develop to the analgesiceffects of therapeutic doses of oxycodone under short-term daily dosing conditions, even though some of its subjective effects may decrease. These data also suggest that intermittent administration may enhance the analgesiceffects of oxycodone, while also increasing some of the drug’s positive subjective effects related to abuse liability. PMID:22495183

Full Text Available Objectives: This study was conducted to clarify the analgesiceffect of toad cake and toad-cake-containing herbal drugs. Methods: We counted the writhing response of mice after the intraperitoneal administration of acetic acid as a nociceptive pain model and the withdrawal response after the plantar surface stimulation of the hind paw induced by partial sciatic nerve ligation of the mice as a neuropathic pain model to investigate the analgesiceffect of toad cake and toad-cake-containing herbal drugs. A co-treatment study with serotonin biosynthesis inhibitory drug 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA, the catecholamine biosynthesis inhibitory drug ?-methyl-DL-tyrosine methyl ester hydrochloride (AMPT or the opioid receptor antagonist naloxone hydrochloride was also conducted. Results: Analgesiceffects in a mouse model of nociceptive pain and neuropathic pain were shown by oral administration of toad cake and toad-cake-containing herbal drugs. The effects of toad cake and toad-cake-containing herbal drugs disappeared upon co-treatment with PCPA, but not with AMPT or naloxone in the nociceptive pain model; the analgesiceffect of toad-cake-containing herbal drugs also disappeared upon co-treatment with PCPA in the neuropathic pain model. Conclusion: Toad cake and toad-cake-containing herbal drugs have potential for the treatments of nociceptive pain and of neuropathic pain, such as post-herpetic neuralgia, trigeminal neuralgia, diabetic neuralgia, and postoperative or posttraumatic pain, by activation of the central serotonin nervous system.

In contemporary post-operative pain management, patients are most often treated with combinations of non-opioid analgesics, to enhance pain relief and to reduce opioid requirements and opioid-related adverse effects. A diversity of combinations is currently employed in clinical practice, and no well-documented 'gold standards' exist. The aim of the present topical, narrative review is to provide an update of the evidence for post-operative analgesic efficacy with the most commonly used, systemic non-opioid drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs)/COX-2 antagonists, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta-analyses, investigating effects of non-opioid analgesics on pain, opioid-requirements, and opioid-related adverse effects. Paracetamol, NSAIDs, COX-2 antagonists, and gabapentin reduced 24?h post-operative morphine requirements with 6.3 (95% confidence interval: 3.7 to 9.0)?mg, 10.2 (8.7, 11.7)?mg, 10.9 (9.1, 12.8)?mg, and???13?mg, respectively, when administered as monotherapy. The opioid-sparing effect of glucocorticoids was less convincing, 2.33 (0.26, 4.39)?mg morphine/24?h. Trials of pregabalin?>?300?mg/day indicated a morphine-sparing effect of 13.4 (4, 22.8)?mg morphine/24?h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX-2 antagonists, and gabapentin all seem to have well-documented, clinically relevant analgesic properties. The analgesiceffects of glucocorticoids and pregabalin await further clarification. Combination regimens are sparsely documented and should be further investigated in future studies. PMID:25124340

In contemporary post-operative pain management, patients are most often treated with combinations of non-opioid analgesics, to enhance pain relief and to reduce opioid requirements and opioid-related adverse effects. A diversity of combinations is currently employed in clinical practice, and no well-documented 'gold standards' exist. The aim of the present topical, narrative review is to provide an update of the evidence for post-operative analgesic efficacy with the most commonly used, systemic non-opioid drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs)/COX-2 antagonists, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta-analyses, investigating effects of non-opioid analgesics on pain, opioid-requirements, and opioid-related adverse effects. Paracetamol, NSAIDs, COX-2 antagonists, and gabapentin reduced 24?h post-operative morphine requirements with 6.3 (95% confidence interval: 3.7 to 9.0)?mg, 10.2 (8.7, 11.7)?mg, 10.9 (9.1, 12.8)?mg, and???13?mg, respectively, when administered as monotherapy. The opioid-sparing effect of glucocorticoids was less convincing, 2.33 (0.26, 4.39)?mg morphine/24?h. Trials of pregabalin?>?300?mg/day indicated a morphine-sparing effect of 13.4 (4, 22.8)?mg morphine/24?h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX-2 antagonists, and gabapentin all seem to have well-documented, clinically relevant analgesic properties. The analgesiceffects of glucocorticoids and pregabalin await further clarification. Combination regimens are sparsely documented and should be further investigated in future studies.

Full Text Available Clinical evaluation of analgesic and anti-inflammatory drugs envisages the development of side effects that makes efficacy of a drug arguable. Alternatively, indigenous drug with fewer side effects is the major thrust area of research in the management of pain and inflammation. In the present study aqueous extract of whole leaf of Aloe vera at various concentrations was investigated for its anti-inflammatory and analgesic activities in albino wistar rats. Carrageenan and formaldehyde-induced rat paw oedema was used to evaluate the anti-inflammatory activity and tail flick, hot plate and acetic acid tests were used to assess the analgesic activity of A. vera leaf aqueous extracts. Whole leaf aqueous extracts at various concentrations (100, 200, 400, and 600 mg/kg of bw significantly reduced formation of oedema induced by carrageenan and formaldehyde and granuloma formation in a dose dependent manner. Further, acetic acid-induced writhing model exhibited significant analgesiceffect characterized by reduction in writhes. Whole leaf aqueous extract showed dose-dependent increase in tolerance to thermal stimulus comparable to indomethacin. No mortality was observed during the acute toxicity test at a dosage of 600mg/kg. Thus whole leaf aqueous extract of Aloe vera can be exploited as non toxic drug for the treatment and clinical management of inflammation and pain.

Full Text Available Objective(sCelecoxib acts through both COX-2-dependent and -independent pathways. According to the paradoxical effect of NO on the inflammatory and nociceptive signal processing, the present study designed to evaluate the probable contribution of NO in the analgesic and anti-inflammatory properties of celecoxib. Materials and MethodsDifferent intensities of inflammatory pain were induced by acute and chronic sc administration of 1%, 2.5%, or 5% formalin and spectrophotometrical analysis of the serum nitrite was performed. Then, in the pretreatment process, the effect of celecoxib (10, 20, or 40 mg/kg/ip was evaluated on the inflammatory pain induced-nitrite. Also, the effect of celecoxib alone (under non-inflammatory condition was evaluated on the peripheral NO production and the results compared with that of the vehicle. ResultsFormalin-induced inflammatory pain led to an enhancement of the serum nitrite in intensity- and time-dependent manners. Celecoxib (40 mg/kg/ip, except its ineffectiveness on the nitrite level, induced 1.5 hr after 5% formalin, reduced production of formalin-induced nitrite in other cases. Meanwhile, under non-inflammatory condition, 1.5 hr after the administration of celecoxib (40 mg/kg/ip, a considerable elevation of nitrite was observed. Celecoxib 10 or 20 mg/kg/ip did not show a significant effect on either inhibition or stimulation of the peripheral NO.ConclusionNO is involved both in the inflammatory and non-inflammatory conditions. It seems that celecoxib exerts a dual effect on the peripheral NO production; it prevents overproduction of NO due to the induction of inflammatory pain, while, it stimulates NO synthesis at the early stage of its action.

Chronic neuroinflammation plays an important role in the development and maintenance of neuropathic pain. The compound flexibilide, which can be obtained from cultured soft coral, possesses anti-inflammatory and analgesiceffects in the rat carrageenan peripheral inflammation model. In the present study, we investigated the antinociceptive properties of flexibilide in the rat chronic constriction injury (CCI) model of neuropathic pain. First, we found that a single intrathecal (i.t.) administration of flexibilide significantly attenuated CCI-induced thermal hyperalgesia at 14 days after surgery. Second, i.t. administration of 10-?g flexibilide twice daily was able to prevent the development of thermal hyperalgesia and weight-bearing deficits in CCI rats. Third, i.t. flexibilide significantly inhibited CCI-induced activation of microglia and astrocytes, as well as the upregulated proinflammatory enzyme, inducible nitric oxide synthase, in the ipsilateral spinal dorsal horn. Furthermore, flexibilide attenuated the CCI-induced downregulation of spinal transforming growth factor-?1 (TGF-?1) at 14 days after surgery. Finally, i.t. SB431542, a selective inhibitor of TGF-? type I receptor, blocked the analgesiceffects of flexibilide in CCI rats. Our results suggest that flexibilide may serve as a therapeutic agent for neuropathic pain. In addition, spinal TGF-?1 may be involved in the anti-neuroinflammatory and analgesiceffects of flexibilide. PMID:24979268

Full Text Available Abstract Background N-type Ca2+ channels (Cav2.2 play an important role in the transmission of pain signals to the central nervous system. ?-Conotoxin (CTx-MVIIA, also called ziconotide (Prialt®, effectively alleviates pain, without causing addiction, by blocking the pores of these channels. Unfortunately, CTx-MVIIA has a narrow therapeutic window and produces serious side effects due to the poor reversibility of its binding to the channel. It would thus be desirable to identify new analgesic blockers with binding characteristics that lead to fewer adverse side effects. Results Here we identify a new CTx, FVIA, from the Korean Conus Fulmen and describe its effects on pain responses and blood pressure. The inhibitory effect of CTx-FVIA on N-type Ca2+ channel currents was dose-dependent and similar to that of CTx-MVIIA. However, the two conopeptides exhibited markedly different degrees of reversibility after block. CTx-FVIA effectively and dose-dependently reduced nociceptive behavior in the formalin test and in neuropathic pain models, and reduced mechanical and thermal allodynia in the tail nerve injury rat model. CTx-FVIA (10 ng also showed significant analgesiceffects on writhing in mouse neurotransmitter- and cytokine-induced pain models, though it had no effect on acute thermal pain and interferon-? induced pain. Interestingly, although both CTx-FVIA and CTx-MVIIA depressed arterial blood pressure immediately after administration, pressure recovered faster and to a greater degree after CTx-FVIA administration. Conclusions The analgesic potency of CTx-FVIA and its greater reversibility could represent advantages over CTx-MVIIA for the treatment of refractory pain and contribute to the design of an analgesic with high potency and low side effects.

Objective: In this study, we aimed comparing early postoperative period analgesiceffectiveness and the effects on opioid consumption of intravenous dexketoprofen and lornoxicam that are given preemptively. Materials and Methods: Forty patients, planned elective mediastinoscopy, were included in this prospective randomized study. These patients were classified in two groups, group D for dexketoprofene trometamol and group L for lornoxicam, randomly. 20 minutes before the operation 50 mg dexke...

Full Text Available Abstract Background Both T-type calcium channels and cannabinoid receptors modulate signalling in the primary afferent pain pathway. Here, we investigate the analgesics activities of a series of novel cannabinoid receptor ligands with T-type calcium channel blocking activity. Results Novel compounds were characterized in radioligand binding assays and in vitro functional assays at human and rat CB1 and CB2 receptors. The inhibitory effects of these compounds on transient expressed human T-type calcium channels were examined in tsA-201 cells using standard whole-cell voltage clamp techniques, and their analgesiceffects in response to various administration routes (intrathecally, intraplantarly, intraperitoneally assessed in the formalin model. A series of compounds were synthesized and evaluated for channel and receptor activity. Compound NMP-7 acted as non-selective CB1/CB2 agonist while NMP4 was found to be a CB1 partial agonist and CB2 inverse agonist. Furthermore, NMP-144 behaved as a selective CB2 inverse agonist. All of these three compounds completely inhibited peak Cav3.2 currents with IC50 values in the low micromolar range. All compounds mediated analgesiceffects in the formalin model, but depending on the route of administration, could differentially affect phase 1 and phase 2 of the formalin response. Conclusions Our results reveal that a set of novel cannabinioid receptor ligands potently inhibit T-type calcium channels and show analgesiceffects in vivo. Our findings suggest possible novel means of mediating pain relief through mixed T-type/cannabinoid receptor ligands.

Harpagophytum procumbens, also known as Devil’s Claw, has historically been used to treat a wide range of conditions, including pain and arthritis. The study was designed to investigate whether H. procumbens extracts exhibit analgesiceffects in plantar incision and spared nerve injury (SNI) rats. The whole procedure was performed on male SD rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT) test measured by von Frey filaments. Pain-related behav...

The 5-HT(3) antagonists tropisetron and granisetron have been shown to block the analgesiceffect of acetaminophen in healthy volunteers. To study the interaction between ondansetron and acetaminophen in women undergoing laparoscopic hysterectomy, we randomized 134 patients into three groups to receive acetaminophen-placebo (AP), acetaminophen-ondansetron (AO), or placebo-placebo (PP). One gram of intravenous acetaminophen or placebo was administered at the induction of anesthesia and every 6 h thereafter for 24 h, and 4 mg of ondansetron or placebo was administered at the end of surgery. Pain control was provided by patient-controlled analgesia (PCA)-oxycodone. Acetaminophen (as compared to placebo) in periodic doses starting at induction of anesthesia reduced the total dosage of oxycodone required over 0-24 h (P = 0.031), but ondansetron given at the end of the surgery had no impact on the analgesiceffect of acetaminophen (P = 0.723). The Numeric Rating Scale (NRS) scores for pain were similar whether ondansetron or placebo was administered at the end of the surgery. Therefore, it may be concluded that in women undergoing laparoscopic hysterectomy, the administration of periodic doses of intravenous acetaminophen (as compared to placebo) starting at induction of anesthesia reduces the total dose requirement of oxycodone, and a concomitant dose of a 5-HT(3) antagonist such as ondansetron at the end of the surgery does not block the analgesiceffect of acetaminophen. PMID:20220746

Full Text Available In this research, hydroalcoholic extract obtained from the aerial parts of Marrubium parviflorum (Lamiaceae was subjected to evaluation of analgesiceffects using formalin test at the doses of 50, 100 and 200 mg kg-1 in mice. Duration of licking and biting time (min of the injected paw was recorded at 5 min intervals for 40 min after formalin injection as a pain index. Results of study showed that the dose of 100 mg kg-1 of the extract decreased duration of licking and biting time between 15 and 40 min, but this effect was not statistically significant (p>0.05, while the dose of 200 mg kg-1 of extract showed significant analgesiceffects (pM. parviflorum as a valuable analgesic herbal medicine that can be used in treatment of inflammatory painful disease. It is possible to assume that phytochemical contents of M. parviflorum reduce inflammatory pain by inhibiting the formation of inflammatory mediators such as prostaglandins followed by inhibiting COX-II enzyme.

Aim: The research was carried out to investigate the analgesic and anti-inflammatory effects of ethanol extract of Desmodium pauciflorum, Mangifera indica and Andrographis paniculata leaves. Materials and Methods: In order to assess the analgesic and anti-inflammatory effects acetic acid induced writhing response model and carrageenan induced paw edema model were used in Swiss albino mice and Wistar albino rats, respectively. In both cases, leaves extract were administered (2gm/kg body weight...

Dysmenorrhoea, defined as cramping pain in the lower abdomen occurring before or during menstruation, affects, to varying degrees, up to 90% of women of child-bearing age. We investigated whether BFP (Bak Foong Pills), a traditional Chinese medicine treatment for dysmenorrhoea, possesses analgesic properties. Results showed that BFP was able to significantly reduce pain responses following subchronic treatment for 3 days, but not following acute (1 h) treatment in response to acetic acid-induced writhing in C57/B6 mice. The analgesiceffect was not due to inhibition of COX (cyclo-oxygenase) activity, evidenced by the lack of inhibition of prostacyclin and PGE2 (prostaglandin E2) production. Molecular analysis revealed that BFP treatment modulated the expression of a number of genes in the spinal cord of mice subjected to acetic acid writhing. RT-PCR (reverse transcription-PCR) analysis of spinal cord samples showed that both sst4 (somatostatin receptor 4) and sst2 receptor mRNA, but not ?OR (?-opiate receptor) and NK1 (neurokinin-1) receptor mRNA, were down-regulated following BFP treatment, thus implicating somatostatin involvement in BFP-induced analgesia. Administration of c-som (cyclo-somatostatin), a somatostatin antagonist, prior to acetic acid-induced writhing inhibited the analgesiceffect. Thus subchronic treatment with BFP has anti-nociceptive qualities mediated via the somatostatin pathway. PMID:21980955

Analgesic consumption poses special risks for regular users of alcohol. Among the numerous adverse health effects are acetaminophen toxicity and gastrointestinal (GI) bleeding associated with nonsteroidal anti-inflammatory drug (NSAID) use. An alcohol-acetaminophen hypothesis contends that alcohol enhances acetaminophen toxicity. Because 22% of adults use acetaminophen each week and 5% to 10% of the population is alcoholic, the healthcare implications of serious adverse interactions are considerable. However, such interactions are rare when NSAID doses remain in the therapeutic range. Although clinical studies fail to support anecdotal case reports of liver damage associated with consumption of therapeutic doses of acetaminophen by alcohol users, such reports are probably inaccurate because of the uncritical acceptance of patient history by the clinician and a lack of well-designed prospective trials. Over-the-counter (OTC) NSAIDs, such as aspirin, naproxen, and ketoprofen, are other analgesic options, but each carries the risk of GI bleeding. Unanswered questions about the newer "second-generation" NSAIDs, such as celecoxib and rofecoxib, make them less desirable than acetaminophen and OTC NSAIDs. Because the risk of GI bleeding or ulceration may be higher in alcoholic patients, the optimal strategy in prescribing pain relievers to those who consume alcohol is to use 1 drug at a time and to clearly communicate its generic name. Acetaminophen is the safest OTC analgesic and is recommended as first-line treatment for osteoarthritis. OTC NSAID users should be carefully advised as to recommended dose, and all patients should be reminded to stay within the dosing limits regardless which OTC analgesic is used. PMID:11776482

Embryo transfer is a surgical technique that is widely used in reproductive biotechnology. Despite the ethical obligation to relieve animals' post-operative pain, analgesia is not routinely provided after embryo transfer surgery because it has been suggested that analgesics may be detrimental to embryo survival. Studies suggest, however, that the potential for adverse effects varies depending on the type of analgesic used and the timing of its administration. The authors carried out a study to determine whether pre-operatively administered tramadol, a synthetic analogue of codeine, influenced birth rate, litter survival or the post-operative body weights of surrogate dams. Compared with controls that were not given any analgesic, surrogate dams given tramadol had similar birth rates and similar body weights at all time points. The tramadol-treated surrogate dams showed a statistically significant increase in the number of offspring that survived to weaning. The authors conclude that pre-operatively administered tramadol does not harm the success rate of embryo transfer surgery and even may improve litter survival. PMID:24751851

Analgesic nephropathy is a slowly progressive disease caused by the chronic abuse of analgesic mixtures containing two analgesic components combined with potentially addictive substances (coffeine and/or codeine). Pathologically, the nephropathy is characterized by renal papillary necrosis with calcification and chronic interstitial nephritis sometimes in association with transitional-cell carcinoma of the uroepithelium. In the early stage, the clinical characteristics are polyuria, sterile pyuria, sometimes renal colic and haematuria. With further progression of the disease, there are the nonspecific symptoms of advanced renal failure. The incidence of classic analgesic nephropathy among Hungarian patients on chronic renal replacement therapy has proven. There is an urgent need for the estimation of analgesic nephropathy among patients with chronic renal disease and among patients with chronic pain presumably regularly taking analgesics in Hungary. As long as analgesic mixtures containing phenacetin or paracetamol and/or nonsteroidal antiinflammatory drugs and addictive substances are available "over-the-counter", analgesic nephropathy will continue to be a problem also in our country. PMID:9846064

Background: Combining different analgesic drugs for improvement of drug efficacy is a recommended strategy intended to achieve the optimal therapeutic effects. Objectives: The purpose of the present study was to assess the nature of the interaction between ascorbic acid and two analgesic drugs, morphine and tramadol. Materials and Methods: The analgesic activity was assessed by the acetic acid writhing test in male Naval Medical Research Institute (NMRI) mice. The results were obtained using four to six animals in each group. All the drugs were injected intraperitoneally. The effective doses (ED) that produced 20%, 50%, and 65% antinociception (ED20, ED50 and ED65) were calculated from the dose-response curve of each drug alone as well as co-administration of ascorbic acid and tramadol or morphine. The interaction index was calculated as experimental ED/theoretical ED. For each drug combination, ED50, ED20 and ED65 were determined by linear regression analysis of the dose-response curve, and they were compared to theoretical ED50, ED20 and ED65 using t-test. Results: The antinociceptive effects of all drugs were dose-dependent (ED50was 206.1 mg/kg for ascorbic acid, 8.33 mg/kg for tramadol, and 0.79 mg/kg for morphine). The interaction index demonstrated additive effects at ED50 and ED65 for co-administration of ascorbic acid and tramadol or morphine. However, at ED20, combination of ascorbic acid and tramadol or morphine showed synergic effects. The interaction index values of the combinations demonstrated the potency ratio of ascorbic acid/morphine to be lower than ascorbic acid/tramadol. Conclusions: This study demonstrated the results of interactions between ascorbic acid and tramadol or morphine. The results showed that the interaction effects on antinociception may be synergistic or additive, depending on the level of effect.

Full Text Available Abstract Background The aim of this study was to investigate the analgesiceffects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesiceffects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms.

Full Text Available This study was performed to evaluate the role of gabapentin co-administration in morphine antinociception and withdrawal effect. Four groups of male rats were examined for latency time using tail flick test; control, morphine (M, gabapentin (GB and gabapentin-morphine (GB-M treated groups. Rats received morphine (10 mg kg < SUP>-1 < /SUP>, s.c. or gabapentin (75 mg kg < SUP>-1 < /SUP>, i.p. or both of them twice a day for 9 days. Control rats received normal saline as schedule time. Latency time was recorded 3 times (5 min of interval before drug injection and in 60, 65 and 70 min after drug injection in days 1, 3, 5, 7 and 9 by tail flick test. Percentage of Maximal Possible Effect (%MPE as antinociceptive effect was calculated for all groups. On 9th day, rats were challenged for withdrawal signs by administration of naloxone (2 mg kg < SUP>-1 < /SUP>, i.p.. Analysis of variance showed no significant difference of %MPE in control and GB groups while in M and GB-M groups the %MPE was changed significantly during the days of study. Gabapentin had no analgesiceffect while morphine and gabapentin-morphine had significant analgesiceffect compared to control. %MPE of GB-M treated rats was significantly higher than M in days 5, 7 and 9. Also this study showed that pre-treatment with gabapentin reduced most of the opioid withdrawal signs including jumping, weight loss and fore paw tremor. The mechanism(s by which gabapentin enhances the analgesiceffect of chronic use of morphine and attenuate opioid withdrawal signs remain to be establish.

This study was intended to evaluate the analgesic and antiinflammatory activities of an aqueous extract of Erigeron floribundus (H.B. & K) or (syn": Conyza sumatrensis (Retz) E.K. Walker) (Asteraceae). Phytochemical analysis was carried out using standard methodologies. The analgesic investigations were carried out against two types of noxious stimuli, chemical (formalin-induced pain and acetic acid-induced writhing) and thermal (hotplate and tail immersion tests). The effects following aspirin and naloxone pretreatments were also studied. For the antiinflammatory activities, the carrageenan-induced oedema of the hindpaw of rats was used and the paw volume measured plethysmometrically from 0 to 24 h after injection. This was compared to a standard drug indomethacin (10 mg/kg). The results were subjected to statistical analysis. The plant had saponins, flavonoids, glycosides, alkaloids, oils, phenols and tannins and significantly increased the reaction time of hotplate and immersion tests. It decreased the writhings of acetic acid-induced abdominal contractions and lickings of formalin-induced pain. Aspirin had no effect on hotplate and tail immersion tests but showed an effect on writhing test. These results showed that the plant had both central and peripheral acting effects and this was confirmed by its effect on both phases of formalin-induced pain. The extract also significantly decreased the rat paw oedema volume at 50 mg/kg and above. In conclusion, Erigeron floribundus has central and peripheralanalgesic properties as well as antiinflammatory activities. PMID:15120453

Pain is a complex unpleasant phenomenon composed of sensory experiences that include time, space, intensity, emotion, cognition and motivation. Analgesics are the agents, which selectively relieve pain by acting in the CNS or by peripheral pain mechanisms without significantly altering consciousness. Analgesics may be narcotic or non-narcotic. The study of pain in animals raises ethical, philosophical and technical problems. Philosophically, there is a problem that pain cannot be monitored di...

Full Text Available Introduction: Sufentanil is a potent but short-acting analgesic that used intrathecally to manage postoperative pain. The goal of study is determining the effect of transdermal nitroglycerine on duration of analgesiceffect of spinal sufentanil in lower extremity surgery .Methods and Material: In a clinical trial study with convenience sampling ASA (I, ASA(IIpatients in 18 -65 old -age condidated for lower extremity surgery in Isfahan st. AlZAHRA medical center in 2001-2002 were randomized to one of four groups. (each group contains ten patients Patients received 15 mg bupivacaine 0.5% plus 2ml of the test drug intrathecally (saline or 10 mic.gram sufentanil. 30 min after the spinal puncture, a transdermal patch of either 5mg nitroglycerinor placebo was applied. The control group (A received spinal saline and transdermal placebo. The sufentanil group (B received spinal sufentanil and transdermal placebo. The nitroglycerine group (C received spinal saline and transdermal nitroglycerine patch. Finally, the sufentanil-nitroglycerine group (D received spinal sufentanil and transdermal nitroglycerine. Pain was evaluated using a 10 - cm visual analog scale. Results were analyzed by ANOVA and chi-square tests.Results:1- The four groups showed no differences regarding ASA, gender, age, weight and height .(P>0.052- Mean and standard deviation of painless time in (B group (268.5 ±59.7 min and (D group (297.7±43.8 min was longer compared with (A group (246.3±4.1 min . (P<0.053- There is no differences regarding mean and standard deviation of painless time between:a (C group (218.5 ± 52.9 min and (A group (246.3 ± 44.1. (P>0.05b (D group (297.7 ± 43.8 min and (B group (268.5 ± 59.7min. (P>0.05c (C group (218.5 ± 52.9 min and (B group (268.5 ± 59.7 min. (P>0.054- Mean and standard deviation of painless time in (D group (297.7 + 43.8 min was longer compard with (Cgroup (218.5 ± 52.9in. (P<0.055-Mean and standard deviation of the pain VAS score was similar among (A group (7.5±1 , (B group (8 ±0.8, (C group (7.2 ± 0.78 and (D group (8 ±0.66. (P>0.056- Mean and standard deviation of changes mean blood pressure 5,10,20,30,40,50,60 min after the spinal injection were also the same in all groups. (P>0.05In this study, respiratory arrest and decrease of consciousness (complicatications of intrathecal opiate was not seen.Conclusion: In the same previus study in Brazil show that transdermal nitroglycerine significantly prolonged the analgsic effect of spinal sufentani (10This study was performed in minor operation. (Arthroscopy (10 That did not cause sever tissue trauma and postoperative pain.(2 (10 Our study showed that: Transdermal nitroglycerine has no effect on prolongation of analgesiceffect of intrathecal sufentanil. Our study performed in patients with osseous fracture that can cause sever tissue trauma and postoperative pain. (probably reason for this difference Also, our study showed that: Transdermal nitroglycerine alone (5mg/day did not result in postoperative analgesia itself.

The objective of the study was to determine the analgesic and systemic effects of subarachnoid administration of xylazine hydrochloride (XY), lidocaine hydrochloride (LI) and their combination (XYLI) in goats. Six healthy goats were used in a prospective randomised study. Three treatments were administered to each goat, with 1-week intervals between each treatment. Treatments consisted of 0.1 mg/kg xylazine, 2.5 mg/kg lidocaine and a combination of xylazine 0.05 (mg/kg) and lidocaine (1.25 mg...

Full Text Available The aim of this study was to evaluate pharmacological properties of ethanol extracted from Mahonia oiwakensis Hayata stems (MOSEtOH. The pharmacological properties included antioxidant, analgesic, anti-inflammatory and hepatoprotective effects. The protoberberine alkaloid content of the MOSEtOH was analyzed by high-performance liquid chromatography (HPLC. The results revealed that three alkaloids, berberine, palmatine and jatrorrhizine, could be identified. Moreover, the MOSEtOH exhibited antioxidative activity using the DPPH assay (IC50, 0.743 mg/mL. The DPPH radical scavenging activity of MOSEtOH was five times higher that that of vitamin C. MOSEtOH was also found to inhibit pain induced by acetic acid, formalin, and carrageenan inflammation. Treatment with MOSEtOH (100 and 500 mg/kg or silymarin (200 mg/kg decreased the serum alanine aminotransferase (ALT and aspartate aminotransferase (AST levels compared with the CCl4-treated group. Histological evaluation showed that MOSEtOH reduced the degree of liver injury, including vacuolization, inflammation and necrosis of hepatocytes. The anti-inflammatory and hepatoprotective effect of MOSEtOH were found to be related to the modulation of antioxidant enzyme activity in the liver and decreases in malondialdehyde (MDA level and nitric oxide (NO contents. Our findings suggest that MOSEtOH has analgesic, anti-inflammatory and hepatoprotective effects. These effects support the use of MOSEtOH for relieving pain and inflammation in folk medicine.

Full Text Available Objective: To study the pharmacological activities and toxicity of the crude alkaloids of Toddalia asiatica and to provide pharmacological data for the further development of this herbal medicine. Methods: We observed the anti-inflammatory effects of the crude alkaloids of Toddalia asiatica, using xylol and agra to induce the turgidness and sodium carboxymethyl cellulose (CMC-Na to induce leucocyte strolling in the rats. The analgesiceffects were observed by body-distortion methods. The effects of alkaloids of Toddalia asiatica on hepatic function were observed by testing the contents of alanine aminotransferase (ALT and aspartate aminotransferase (AST in serum and calculating the liver index. The LD50 and 95% creditability were calculated with developed Karber Method. Results: The administration of alkaloids of Toddalia asiatica had the function of inhibiting the auricle swelling caused by xylol and joint swelling caused by agar and leucocyte migration caused by CMC-Na, decreasing the body-distortion of the rats. After two-week administration, the contents of ALT and AST showed that there was no obvious difference between administered group and control group. The LD50 of the crude alkaloids of Toddalia asiatica was 1.622 g/kg and the 95% creditability was 1.29-2.03 g/kg. Conclusion: Toddalia asiatica has anti-inflammatory and analgesiceffects, and there is no injury to the liver after long-term administration in rats

Full Text Available We conducted a double blind, controlled trial comparing postoperative analgesiceffect of tramadol with lidocaine when used as subcutaneous local anesthetic. Seventy ASA physical status 1 or 2 patients aged 20-50 years, who were scheduled for elective surgery under general anesthesia with flank incision, were randomly assigned to receive either 2 mg kg-1 tramadol or 1 mg kg-1 lidocaine at the end of operation. Postoperative pain was evaluated with a Verbal Analogue Scale (VAS. First VAS and patient’s satisfaction with operation were recorded at recovery room, second record was in the ward (12 h later and third on the next day of surgery (24 h later. Local reactions, nausea and vomiting in recovery and the ward and time to first request for analgesic after operation were also recorded. Satisfaction with operation in recovery room was better in tramadol group (p = 0.016. The VAS score did not differ significantly between the two groups in recovery (p = 0.119, 12 h (p = 0.316 and 24 h after the operation (p = 0.108. Time to first analgesic requirement in tramadol group was longer (4.3±0.3 h than lidocaine group (2.1±0.9 h (p = 0.012. Ten patients in tramadol and 2 in lidocaine group had nausea in recovery room (p = 0.01. Eight and three patients had nausea in the ward, respectively (p = 0.101. There was not significant difference in vomiting between two groups in the recovery and the ward (p = 0.106 and p = 0.112, respectively. No local reactions were recorded in either group. This study showed that subcutaneous administration of tramadol provided local anesthesia equal to lidocaine with longer pain-free period after operation.

Full Text Available Aim: The research was carried out to investigate the analgesic and anti-inflammatory effects of ethanol extract of Desmodium pauciflorum, Mangifera indica and Andrographis paniculata leaves. Materials and Methods: In order to assess the analgesic and anti-inflammatory effects acetic acid induced writhing response model and carrageenan induced paw edema model were used in Swiss albino mice and Wistar albino rats, respectively. In both cases, leaves extract were administered (2gm/kg body weight and the obtained effects were compared with commercially available analgesic and anti-inflammatory drug Dclofenac sodium (40mg/kg body weight. Distilled water (2ml/kg body weight was used as a control for the study. Results: In analgesic bioassay, oral administration of the ethanol extract of leaves were significantly (p<0.01 reduced the writhing response. The efficacy of leaves extract were almost 35% in Desmodium pauciflorum, 56% in Mangifera indica and 34% in Andrographis paniculata which is found comparable to the effect of standard analgesic drug diclofenac sodium (76%. Leaves extract reduced paw edema in variable percentages but they did not show any significant difference among the leaves. Conclusion: We recommend further research on these plant leaves for possible isolation and characterization of the various active chemical substances which has the toxic and medicinal values. [Vet World 2013; 6(2.000: 68-71

The solubilizing and absorption enhancer properties towards naproxen of chitosan and polyvinylpyrrolidone (PVP) have been investigated. Solid binary systems prepared at various drug-polymer ratios by mixing, cogrinding or kneading, were characterized by differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, and scanning electron microscopy, and tested for dissolution behavior. Both carriers improved drug dissolution and their performance depended on the drug-polymer ratio and the system preparation method. Chitosan was more effective than PVP, despite the greater amorphizing power of PVP as revealed by solid state analyses. The 3/7 (w/w) drug-carrier coground systems with chitosan and PVP were the best products enabling, respectively, an improvement of 4.8 and 3.6 times of drug dissolution efficiency. In vivo experiments in mice demonstrated that administration of 45 mg/kg of drug coground with PVP or chitosan resulted, respectively, in a 25 and 60% reduction of acetic acid-induced writhings in comparison to pure drug, which, instead, was statistically ineffective as compared to the control group. Moreover, the 3/7 (w/w) drug-chitosan coground product demonstrated an antiwrithing potency 2.4 times higher than the coground with PVP. Thus, the direct-compression properties and antiulcerogenic activity, combined with the demonstrated solubilizing power and analgesiceffect enhancer ability towards the drug, make chitosan particularly suitable for developing a reduced-dose fast-release solid oral dosage form of naproxen. PMID:14729084

Harpagophytum procumbens, also known as Devil's Claw, has historically been used to treat a wide range of conditions, including pain and arthritis. The study was designed to investigate whether H. procumbens extracts exhibit analgesiceffects in plantar incision and spared nerve injury (SNI) rats. The whole procedure was performed on male SD rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT) test measured by von Frey filaments. Pain-related behavior was also determined through analysis of ultrasonic vocalization (USVs). The results of experiments showed MWT values of the group that was treated with 300 mg/kg H. procumbens extract increased significantly; on the contrary, the number of 22-27 kHz USVs of the treated group was reduced at 6 h and 24 h after plantar incision operation. After 21 days of continuous treatment with H. procumbens extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity responses by MWT, compared with the control group. These results suggest that H. procumbens extracts have potential analgesiceffects in the case of acute postoperative pain and chronic neuropathic pain in rats. PMID:24441655

Full Text Available Harpagophytum procumbens, also known as Devil’s Claw, has historically been used to treat a wide range of conditions, including pain and arthritis. The study was designed to investigate whether H. procumbens extracts exhibit analgesiceffects in plantar incision and spared nerve injury (SNI rats. The whole procedure was performed on male SD rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT test measured by von Frey filaments. Pain-related behavior was also determined through analysis of ultrasonic vocalization (USVs. The results of experiments showed MWT values of the group that was treated with 300 mg/kg H. procumbens extract increased significantly; on the contrary, the number of 22–27 kHz USVs of the treated group was reduced at 6 h and 24 h after plantar incision operation. After 21 days of continuous treatment with H. procumbens extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity responses by MWT, compared with the control group. These results suggest that H. procumbens extracts have potential analgesiceffects in the case of acute postoperative pain and chronic neuropathic pain in rats.

The current study was designed to develop a topical gel formulation for improved skin penetration of lornoxicam (LOR) for enhancement of its analgesic activity. Moreover, the effect of different penetration enhancers on LOR was studied. The LOR gel formulations were prepared by using hydroxylpropyl methylcellulose (HPMC) and carbopol. The carbopol gels in presence of propylene glycol (PG) and ethanol were developed. The formulated gels were characterized for pH, viscosity, and LOR release using Franz diffusion cells. Also, in vitro skin permeation of LOR was conducted. The effect of hydroxypropyl ?-cyclodextrin (HP ?-CD), beta-cyclodextrin (?-CD), Tween 80, and oleic acid on LOR permeation was evaluated. The optimized LOR gel formulation (LORF8) showed the highest flux (14.31 ?g/cm(2)/h) with ER of 18.34 when compared to LORF3. Incorporation of PG and HP ?-CD in gel formulation (LORF8) enhanced the permeation of LOR significantly. It was observed that LORF3 and LORF8 show similar analgesic activity compared to marketed LOR injection (Xefo). This work shows that LOR can be formulated into carbopol gel in presence of PG and HP ?-CD and may be promising in enhancing permeation. PMID:25045724

The pharmacokinetics and analgesiceffect of the nonsteroidal anti-inflammatory drug meloxicam (0.5?mg/kg) in goats were investigated. In a randomized, cross-over design the pharmacokinetic parameters were investigated in adult goats (n?=?8) after single intravenous and oral administration. The analgesiceffect was evaluated in kids using a randomized, placebo controlled and blinded protocol. Kids received meloxicam (n?=?6) once daily and their siblings (n?=?5) got isotonic NaCl intramuscularly while still anaesthetized after cautery disbudding and injections were repeated on three consecutive days. In the adult goats after intravenous administration the terminal half-life was 10.9?±?1.7?h, steady-state volume of distribution was 0.245?±?0.06?L/kg, and total body clearance was 17.9?±?4.3?mL/h/kg. After oral administration bioavailability was 79?±?19%, C(max) was 736?±?184?ng/mL, T(max) was 15?±5?h, although the terminal half-life was similar to the intravenous value, 11.8?±?1.7?h. Signs of pain using a visual analogue scale were smaller in kids treated with meloxicam compared with kids treated with placebo on the first day after disbudding, but subsequently no difference in pain was noticeable. Plasma cortisol and glucose concentrations did not differ between the two groups. PMID:21219346

Results: The leaf extract of Nyctanthes arbor-tristis produced significant analgesic activity in a dose dependent manner (both peripheral and central at doses 200 mg/kg and 400 mg/kg. But when compared to the standard drugs (aspirin for peripheral analgesia and pethidine for central analgesia the efficacy of the test drug was found to be inferior even at highest dose (400 mg/kg. The onset of action of the test drug was found to be between 30 minutes to one hour and duration of action was up to three hours in central analgesia and significant peripheral analgesia was seen even after four hours of administration of NALE at 400 mg/kg dose. Conclusion: This study demonstrates the potential analgesiceffect of Nyctanthes arbor-tristis leaf which supports the claim of traditional medicine practitioners. [J Intercult Ethnopharmacol 2013; 2(2.000: 105-112

Full Text Available Aridanin (an N-acetylglycoside of oleanolic acid isolated from Tetrapleura tetraptera fruit was investigated for anticonvulsant, analgesic and hypothermic activities in mice. Aridanin at doses of 15 and 30 mg kg-1 by intraperitoneal administration was shown to protect animals in pentylenetetrazole (PTZ-induced seizure but not in strychnine and picrotoxin induced convulsions. The same dose of aridanin equally decreased rectal temperature and acetic acid-induced writhes in mice. The hypothermic action of aridanin was reversed by pretreatment with cyproheptadine (0.1 mg kg-1, atropine (2 mg kg-1, naltrexone (0.25 mg kg-1, but not with haloperidol (0.1 mg kg-1. The effect on acetic acid-induced writhes was completely blocked by naltrexone, but not by atropine, cyproheptadine and haloperidol. The results suggest that aridanin could be acting as a Central Nervous System (CNS depressant and that its anticonvulsant property is mediated through the membrane stabilizing property and not through GABA and glycine neurotransmitters respectively. Analgesic and hypothermic actions were mediated through opioids and cholinergic, 5-HT receptors, respectively.

Full Text Available "nThe quality of subarachnoid block can be improved by adding opioids to the local anesthetics. We compared the analgesiceffects of different doses of intrathecal sufentanil added to lidocaine %5 for elective cesarean section. This study was a prospective, randomized, double-blind, controlled trial. 90 pregnant women with ASA class I-II, scheduled for elective cesarean section under spinal anesthesia were enrolled in this study. Three groups were made of them by random; Group 1 (control group was given lidocaine 5% (75 mg and 2 ml of normal saline. Patients in Group 2 received lidocaine 5% (75 mg and 5 micrograms sufentanil plus 1ml normal saline. Group 3 patients received lidocaine 5% (75 mg and 10 micrograms sufentanil. Duration of sensory block and effective analgesia (need to analgesic were measured. Opioid related side effects were recorded. Duration of sensory block and effective analgesia were prolonged in sufentanil groups in comparison of control group(50.3±4 that was significantly more in group3 (128 ± 4 versus group 2 (58.3 ± 10(P < 0.001 . There was mild to moderate respiratory depression in sufentanil groups which was more noted in group 3 (p < 0.001. No differences were detected in other side effects such as hypotension, nausea & vomiting. The addition of sufentanil 10 versus 5 micrograms to lidocaine 5% provided more duration of analgesia for cesarean delivery. So, the adding of 10 micrograms sufentanil to lidocaine 5% for cesarean section has more effective analgesia with minimum side effects.

Full Text Available Intrathecal administration of midazolam has been reported to have antinociceptive action, and to be an effectiveanalgesic agent. In this prospective double-blind study we aimed to evaluate the postoperative effects of intrathecal midazolam with lidocaine following perineal operation. Forty patients were randomly allocated to two groups: 20 patients in the control group received 2 ml of 5% heavy lidocaine plus 0.4 ml of 0.9% saline intrathecally; 20 patients in the midazolam group received 2 ml of 5% heavy lidocaine plus 0.4 ml of 0.5% midazolam. Duration of analgesia was significantly greater in the midazolam group (7 ? 1 hours compared to the control group (1.5 ? 0.5 hours.

This prospective, randomized, placebo-controlled study evaluated the effects of dexketoprofen as an adjunct to lidocaine in intravenous regional anaesthesia (IVRA) or as a supplemental intravenous (i.v.) analgesic. Patients scheduled for elective hand or forearm soft-tissue surgery were randomly divided into three groups. All 45 patients received 0.5% lidocaine as IVRA. Dexketoprofen was given either i.v. or added into the IVRA solution and the control group received an equal volume of saline both i.v. and as part of the IVRA. The times of sensory and motor block onset, recovery time and postoperative analgesic consumption were recorded. Compared with controls, the addition of dexketoprofen to the IVRA solution resulted in more rapid onset of sensory and motor block, longer recovery time, decreased intra- and postoperative pain scores and decreased paracetamol use. It is concluded that coadministration of dexketoprofen with lidocaine in IVRA improves anaesthetic block and decreases postoperative analgesic requirements. PMID:22117995

Full Text Available Abstract Background The cholinergic and opioid systems play important roles in modulating inflammation. This study tests whether auricular acupuncture (AA produces anti-inflammatory effects via opioid and peripheral cholinergic receptors in a rat model. Methods Rats were anesthetized with chloral hydrate and inflammation was induced by intraplantar injection of carrageenan. Electroacupuncture was performed at auricular points bilaterally. The severity of inflammation was assessed using changes in paw volume and thermal and mechanical pain thresholds of the rats during recovery from anesthesia. Results Electroacupuncture at selected auricular acupoints significantly reduced paw edema and mechanical hyperalgesia, with no significant effect on thermal hyperalgesia. The anti-edematous and analgesiceffects of AA were abolished by blockade of peripheral cholinergic muscarinic receptors with methyl atropine. Blockade of local muscarinic receptors at the inflamed site with a small dose of atropine also antagonized the anti-edematous effect of AA. By contrast, systemic opioid receptor blockade with naloxone did not antagonize the anti-inflammatory effects of AA. Conclusion This study discovers a role of peripheral muscarinic receptors in mediating the anti-inflammatory effects of AA. The cholinergic muscarinic mechanism appears to be more important than the opioid mechanism in the anti-inflammatory action of AA.

The sensation of pain arises through stimulation of peripheral nociceptors and is transmitted centrally involving several receptors and ion channels. In addition many endogenous physiologic pain-modulating mechanisms exist. Besides of classical analgesics, numerous other drugs showed analgesic properties based on diverse modes of actions along the pain pathway. These co-analgesics, administered in combination with classical drugs, are able to reduce painful states of different origin. We describe the peripheral action sites of co-analgesics, such as cannabinoids, capsaicin, bisphosphonates, steroids and somatostatin. We also summarise the effect of peripherally and centrally acting ion-channel blockers, e.g. local anaesthetics, carbamazepine and tolperisone working on sodium channels and gabapentin and pregabalin working on calcium channels. Finally, central analgesic mechanisms are discussed, for instance the inhibition of NMDA-receptors by ketamine or magnesium, the stimulation of alpha2-receptors by clonidine, tizanidine or antidepressants, the activation of GABA-receptors through baclofen and other analgesic mechanisms of i.e. ondansetron and neostigmine. PMID:19918705

The perioperative care of obstructive sleep apnea (OSA) patients is currently receiving much attention due to an increased risk for complications. It is established that postoperative changes in sleep architecture occur and this may have pathophysiological implications for OSA patients. Upper airway muscle activity decreases during rapid eye movement sleep (REMS). Severe OSA patients exhibit exaggerated chemoreceptor-driven ventilation during non-rapid eye movement sleep (NREMS), which leads to central and obstructive apnea. This article critically reviewed the literature relevant to preoperative screening for OSA, prevalence of OSA in surgical populations and changes in postoperative sleep architecture relevant to OSA patients. In particular, we addressed three questions in regard to the effects of sedative-hypnotics, anesthetics and analgesics on sleep architecture, the underlying mechanisms and the relevance to OSA. Indeed, these classes of drugs alter sleep architecture, which likely significantly contributes to abnormal postoperative sleep architecture, exacerbation of OSA and postoperative complications. PMID:25318836

Full Text Available Previous studies report that the ingestion of highly concentrated sweet solutions produces a morphine-like analgesia in rats, human infants, and in adult males. To determine whether sweet-induced analgesia occurs with more commonly consumed substances, 30 adult males (Mage = 22.4 years were exposed to a cold pressor test and pain responsivity was assessed both before and after consuming either an 8% sucrose solution, water, or nothing. Between-groups comparisons revealed that relative to the Sucrose or Nothing groups, the Water group showed increased pain tolerance. Neither pain thresholds nor ratings of pain intensity and unpleasantness on a visual analogue scale differed among groups. The results support previous findings in both humans and animals that the palatability or hedonic value of food or drink may be the key predictor of its analgesiceffect.

Full Text Available SciELO Brazil | Language: English Abstract in english The objective of the study was to compare the analgesiceffectiveness of dexamethasone and diclofenac sodium administered preemptively after surgical removal of third molars. Forty-four ASA (American Society of Anesthesiologists) I patients (19 men, 35 women; 16–28 years old) randomly and double-bli [...] ndly received diclofenac sodium (50?mg) or dexamethasone (8?mg) or placebo 1?h before surgery. Intensity of pain, measured with a visual analog scale (VAS), was the variable studied at different postoperative times (1?h, 2?h, 3?h, 6?h, 8?h, 12?h, 48?h, 4?d and 7?d). The total amount of rescue medication (TARM) ingested (paracetamol) was another variable of the study. The Kruskal-Wallis statistical test was used. A p value of

Full Text Available Hibiscus populnea or Indian Tulip Tree or Pacific Rosewood, has been traditionally used for thetreatment of many diseases including inflammatory conditions. A number of chemical constituentsnamely, thespesin, gossypol, DL-gossypol, populnin, populneol, glycosides of quercetin, epoxylic acid,rutin, kaemferol-3-flucoside, lupenone, mansonone, myricyl alcohol, lipids and ? sitosterol have beenisolated from the plant. Many of these compounds are proved to have the claimed activities. But nowork has been specifically carried out to establish the anti inflammatory effects of the ripe and olderleaves. Hence in the present study an attempt was made, with the leaves, for the phytochemicalscreening of the methanol, pet. ether and aqueous extracts along with their anti-inflammatory andanalgesic potential also. In order to study the anti-inflammatory effects, dextran-induced paw edemamethod and carrageenan - induced paw edema methods were used. Similarly analgesic activity wastested using acetic acid writhing. Anti arthritic study was also tried. Regarding carrageenan- inducedpaw edema, the level of activity of the petroleum ether extract was less than that of the reference drugand the methanolic extract exhibited the most potent inhibitory activity. But the activity of the aqueousextract was more than that of Indomethacin. From the results of the experimentally induced arthriticstudy it was seen that the activity of the petroleum ether extract was quite stable throughout the period ofassay where as the methanolic extract was proved to be more active against the chronic phase thanagainst the acute phase. The aqueous extract was seen to be a very potent anti inflammatory agentagainst both phases of the inflammatory process with more or less the same activity as that ofindomethacin, the reference standard. The analgesic activities of aqueous and methanolic extracts werefound to be very significant (P < 0.001.

Affective states are regulated mainly by serotonin and noradrenaline. However the opioid system has been also related to antidepressant-induced mood improvement, and the mu-opioid receptor has been involved in affective responses to a sustained painful stimulus. Similarly, antidepressant drugs induce an antinociceptive effect via both the monoaminergic and opioid systems, probably involving sensorial and affective dimensions of pain. The aim of this study was to test three opiate analgesics, which also inhibit monoamine reuptake, in the learned helplessness model of depression in rats. Helpless rats receiving (+/-)tramadol (10, 20 mg/Kg) or (-)methadone (2, 4 mg/Kg) showed a decreased number of failures to avoid or escape aversive stimulus (shock) in both the second and the third daily sessions, compared with controls. Rats receiving levorphanol (0.5, 1 mg/Kg) showed a decreased number of such failures in the third session. The number of crossings in the intertrial interval (ITI) was not significantly modified by (+/-)tramadol or (-)methadone. Levorphanol enhanced ITI crosses at 1 mg/Kg. These results, together with other clinical and experimental data, suggest that analgesics with monoaminergic properties improve mood and that this effect may account for their analgesiceffect in regulating the affective dimension of pain. From this, it seems probable that the analgesiceffect of opiates could be induced by adding together the attenuation produced of both the sensorial and the affective dimensions of pain. PMID:12417248

What this paper adds What is already known about this subject • Pregabalin is an anticonvulsive agent prescribed as a secondary analgesic for patients when standard pain treatment is insufficient. • The analgesiceffect resides to the central nervous system. • The central analgesiceffect can be evaluated by electroencephalographic. What this study adds • The analgesiceffect of pregabalin is reflected as a slowing of brain oscillations. • The slowing of brain oscillations for each individual patient is correlated to subjective pain scores. • The developed methodology may be used as a mechanistic approach to monitor the analgesiceffect of pregabalin in pharmacological studies. SUMMARY: Aim: To identify electroencephalographic (EEG) biomarkers for the analgesiceffect of pregabalin in patients with chronic visceral pain. Methods: This was a double-blind, placebo-controlled study in thirty-one patients suffering from visceral pain due to chronic pancreatitis. Patients received increasing doses of pregabalin (75mg-300mg twice a day) or matching placebo during 3 weeks of treatment. Pain scores were documented in a diary based on the visual analogue scale. In addition, brief pain inventory-short form (BPI) and quality of life questionnaires were collected prior to and after the study period. Multi-channel resting EEG was recorded before treatment onset and at the end of the study. Changes in EEG spectral indices were extracted, and individual changes were classified by a support vector machine (SVM) to discriminate the pregabalin and placebo responses. Changes in individual spectral indices and pain scores were correlated. Results: Pregabalin increased normalized intensity in low spectral indices, most prominent in the theta band (3.5-7.5Hz), difference of -3.18, 95%CI -3.57, -2.80; P = 0.03. No changes in spectral indices were seen for placebo. The maximum difference between pregabalin and placebo treated patients were seen in the parietal region, with a classification accuracy of 85.7% (P = 0.009). Individual changes in EEG indices were correlated to changes in pain diary (P = 0.04) and BPI pain composite scores (P = 0.02). Conclusions: Changes in spectral indices caused by slowing of brain oscillations were identified as a biomarker for the central analgesiceffect of pregabalin. The developed methodology may provide perspectives to assess individual responses to treatment in personalized medicine.

Clinicians in acute care settings are often called upon to manage cancer pain unrelieved by medications. Cognitive-behavioral strategies, such as relaxation and imagery, are recommended for cancer pain management; however, there appear to be individual differences in their effects. This pilot study examined variation in pain outcomes achieved with progressive muscle relaxation (PMR) and analgesic imagery interventions among hospitalized patients with cancer pain, and assessed the influence of four individual difference variables (cognitive ability, outcome expectancy, previous experience, and concurrent symptoms) on pain relief achieved with each intervention. A crossover design was used in which 40 hospitalized cancer patients received two trials of PMR, two trials of analgesic imagery, and two trials of a control condition. In comparing means between treatment and control conditions, both PMR and analgesic imagery produced greater improvements in pain intensity, pain-related distress, and perceived control over pain than the control condition. However, individual responder analysis revealed that only half of the participants achieved a clinically meaningful improvement in pain with each intervention. Patients who achieved a meaningful improvement in pain with analgesic imagery reported greater imaging ability, more positive outcome expectancy, and fewer concurrent symptoms than those who did not achieve a meaningful reduction in pain. Similar relationships were not significant for the PMR intervention. Investigators should continue efforts to identify factors that moderate the effects of cognitive-behavioral pain coping strategies so that clinicians can identify the most beneficial treatments for individual patients. PMID:18504089

A benzensulfonanilide-type cyclooxygenase-1 (COX-1)-selective inhibitor, ZXX2-77: 4-amino-4'-chloro-N-methylbenzenesulfonanilide (4a), has been reported as a novel analgesic that does not cause gastric damage. This compound has a weak analgesiceffect but has potent in vitro COX-1 inhibitory activity. Since the reason for the weak analgesiceffect in vivo was thought to be the low rate of oral absorption, the blood concentration of ZXX2-77 (4a) was measured in rats. It was found that the C(max) value (1.2 microM) of ZXX2-77 (4a) at a dose of 30 mg/kg did not reach the COX-1 IC(50) value (3.2 microM). On the other hand, ZXX2-79 (4b) (SO(2)NH derivative of ZXX2-77 (4a); 4-amino-4'-chlorobenzenesulfonanilide), which shows less potent COX inhibitory activities (COX-1 IC(50) = 12 microM, COX-2 IC(50) = 150 microM) than those of ZXX2-77 (4a) in vitro, was found to be more absorbable (C(max) = 16 microM at a dose of 30 mg/kg in rats) than ZXX2-77 (4a). Furthermore, ZXX2-79 (4b) not only showed a potent analgesiceffect in a formalin test but also caused little gastric damage. These findings indicate that demethylated sulfonamide compounds are more easily absorbed than are N-methylated sulfonamide compounds and suggest that COX-1-selective inhibitors will be useful as analgesics that do not cause gastric damage. PMID:18452178

We studied the effect of the location of electrical stimulation on the acute analgesic response to percutaneous neuromodulation therapy in patients with nonradiating neck pain. Sixty-eight patients received three different nonpharmacologic modalities, namely "needles only" (neck), local (neck) dermatomal stimulation, and remote (lower back) dermatomal stimulation in a random sequence over the course of an 11-wk study period. All treatments were given for 30 min, 3 times per week for 3 wk, with 1 wk "off" between each modality. The assessment tools included the health status survey short form (SF-36) questionnaire, as well as 10-cm visual analog scales for assessing pain, physical activity, and quality of sleep. The pain visual analog scale was repeated 5-10 min after each treatment session. The daily oral nonopioid analgesic requirements were recorded in the patient diary during the entire study period. At the end of each 3-wk treatment block, the SF-36 questionnaire was repeated. Compared with needles only and remote dermatomal stimulation, local dermatomal stimulation produced a significantly greater decrease in pain (38%+/-17% vs 9%+/- 16% and 13%+/-18%), increase in physical activity (41%+/-21% vs 11% +/-17% and 16%+/-15%), and improvement in the quality of sleep (34% +/-18% vs 7%+/-17% and 10%+/-18%) compared with baseline values (Premote dermatomal stimulation, respectively. The posttreatment SF-36 test results revealed that all three modalities produced improvements compared with the prestudy scores for both the physical component summary and mental component summary. However, the magnitude of the changes in the physical component summary and mental component summary with local dermatomal stimulation was significantly greater (+7.9 and +3.6, respectively) than needle only (+3.4 and +1.7, respectively) or remote dermatomal stimulation (+3.7 and +1.9, respectively). No side effects were reported at the needle insertion sites. We conclude that electrical stimulation at the specific dermatomal levels corresponding to the local pathology produces greater short-term improvements in pain control, physical activity, and quality of sleep in patients with chronic neck pain. PMID:11004055

This research is a preliminary study conducted to determine the effects of aspirin (acetyl-salicylic acid) and salicylic acid (analgesics and their derivatives) on the antibiotic resistance of ammonia oxidizing bacterium (AOB) (a non-pathogenic environmental microbe) cultured from the Texas Tech University-Water Recovery System that treats a space related wastewater for NASA. The effect of salicylic acid was investigated by obtaining the minimal inhibition concentration (MIC) of antibiotics (amoxicillin, ciprofloxacin, and nalidixic acid) in the presence of aspirin and salicylic acid. The possibility of transfer of resistance genes between unrelated species was investigated by analyzing the similarity of the AcrA protein (a multi-drug efflux protein) in Nitrosomonas europaea, Escherichia coli and Salmonella enterica. The protein alignment analysis was done using ExPASy, a proteomics tool. The results of this preliminary study indicated that the antibiotic resistance of AOBs increased in the presence of aspirin and salicylic acid and similarities in the AcrA protein of different species indicated the likelihood of possible resistance transfer between the species. This paper high lights the importance of research and further investigation on antibiotic resistance and resistance transfer, highlighting the number of parameters that should be considered while assessing antibiotic resistance in environmental samples. PMID:19448319

The objective of this study was to compare the postoperative analgesiceffects of dexketoprofen, tramadol, and buprenorphine in dogs undergoing ovariohysterectomy. Seventy-five adult female dogs were randomly assigned to receive an intravenous injection (IV) of 1mg/kg of dexketoprofen (D), 0.02 mg/kg of buprenorphine (B) or 2mg/kg of tramadol (T). Pain assessment was performed during 48 h after ovariohysterectomy using a dynamic interactive visual analogue scale (DIVAS) and Glasgow composite measure pain scale (CMPS-SF). Rescue analgesia was required in 43%, 21%, and 5% of dogs in the B, T, and D groups, respectively, with significant differences between B and D (p=0.010) groups. The DIVAS and CMPS-SF values of the B group were significantly higher than those of the T and D groups. The most common undesirable effect was dysphoria in dexketoprofen group. Tramadol and dexketoprofen provide superior postoperative analgesia compared with buprenorphine in dogs undergoing ovariohysterectomy. PMID:23562407

The prefrontal cortex may be a promising target for transcranial magnetic stimulation (TMS) in the management of pain. It is not clear how prefrontal TMS affects pain perception, but previous findings suggest that ventral lateral and medial prefrontal circuits may comprise an important part of a circuit of perceived controllability regarding pain, stress, and learned helplessness. Although the left dorsolateral prefrontal cortex is a common TMS target for treating clinical depression as well as modulating pain, little is known about whether TMS over this area may affect perceived controllability. The present study explored the immediate effects of fast TMS over the left dorsolateral prefrontal cortex on the analgesiceffects of perceived pain controllability. Twenty-four healthy volunteers underwent a laboratory pain task designed to manipulate perception of pain controllability. Real TMS, compared with sham, suppressed the analgesic benefits of perceived control on the emotional dimension of pain, but not the sensory/discriminatory dimension. Findings suggest that, at least acutely, fast TMS over the left dorsolateral prefrontal cortex may interrupt the perceived-controllability effect on the emotional dimension of pain experience. Although it is not clear whether this cortical area is directly involved with modulating perceived controllability or whether downstream effects are responsible for the present findings, it appears possible that left dorsolateral prefrontal TMS may produce analgesiceffects by acting through a cortical perceived-control circuit regulating limbic and brainstem areas of the pain circuit. Despite evidence that prefrontal TMS can have analgesiceffects, fast left prefrontal TMS appears to acutely suppress analgesia associated with perceived-control. This effect may be limited to the emotional dimension of pain experience. PMID:21122992

The 5-HT(4) receptor agonist tegaserod (TEG) has been reported to modulate visceral pain. However, the underlying mechanism remains unknown. The objective of the present study was to examine the analgesic mechanism and site of action of TEG. In male rats, visceral pain was assessed by measuring visceromotor response (VMR) to colorectal distension (CRD). Inflammation was induced by intracolonic injection of tri-nitrobenzene sulfonic acid (TNBS). The effect of TEG on the VMR was tested by injecting intraperitoneal (i.p.), intrathecal (i.t.), intracerebroventricular (i.c.v) or in the rostroventral medulla (RVM). The effect of the drug was also tested on responses of CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons. Systemic injection of TEG attenuated VMR in naive and TNBS-treated rats. Similarly, supraspinal, but not spinal, injection of TEG attenuated the VMR. While GR113808, (selective 5-HT(4) antagonist) blocked the effect, naloxone (NLX) an opioid receptor antagonist reversed the effect of TEG. Although i.t. NLX did not block the inhibitory effect of TEG in VMR study, i.t. injection of ?2-adrenergic receptor antagonist yohimbine blocked the effect of TEG when given systemically. While TEG had no effect on the responses of CRD-sensitive PNA, it inhibited the responses of CRD-sensitive LS neurons in spinal intact condition. This inhibition was blocked by GR113808, NLX and ?-funaltrexamine (?-FNA) when injected into the RVM. Results indicate that TEG produces analgesia via activation of supraspinal 5-HT(4) receptors which triggers the release of opioids at supraspinal site, which activates descending noradrenergic pathways to the spinal cord to produce analgesia. PMID:24334068

This study was performed to evaluate the sedative and analgesiceffects of xylazine (X) and tramadol (T) intravenously (IV) administered to horses. Six thoroughbred saddle horses each received X (1.0 mg/kg), T (2.0 mg/kg), and a combination of XT (1.0 and 2.0 mg/kg, respectively) IV. Heart rate (HR), respiratory rate (RR), rectal temperature (RT), indirect arterial pressure (IAP), capillary refill time (CRT), sedation, and analgesia (using electrical stimulation and pinprick) were measured before and after drug administration. HR and RR significantly decreased from basal values with X and XT treatments, and significantly increased with T treatment (p sedation and analgesia were approximately 5 min after both X and XT treatments; however, the XT combination produced a longer duration of sedation and analgesia than X alone. Two horses in the XT treatment group displayed excited transient behavior within 5 min of drug administration. The results suggest that the XT combination is useful for sedation and analgesia in horses. However, careful monitoring for excited behavior shortly after administration is recommended. PMID:21897102

Full Text Available Osteoarthritis (degenerative joint disease is the most common joint disorder. It mostly affects cartilage. The top layer of cartilage breaks down and wears away. Osteoarthritis is of two types, primary (idiopathic and secondary. In idiopathic osteoarthritis, the most common form of the disease, no predisposing factor is apparent. Secondary OA is pathologically indistinguishable from idiopathic OA but is attributable to an underlying cause. The NSAID’S are main drug of choice in modern medicine which have lots of side effect therefore are not safe for long term therapy. Raktamokshan viz bloodletting is one of the ancient and important parasurgical procedure described in Ayurveda for treatment of various diseases. Of them, Jalaukavacharana or Leech Therapy has gained greater attention globally, because of its medicinal values. The saliva of leech contains numerous biologically active substances, which has anti-inflammatory, analgesic as well as anesthetic property. Keeping this view in mind we have started leech therapy in the patients of osteoarthritis and found encouraging results.

Introduction: Nowadays, many researches are being conducted in order to evaluate the analgesiceffects of different plants which have been used as sedative in traditional medicine. Solanum Melongena is a plant with different theories about its analgesiceffects. In this experimental trial research, the effects of intraperitoneal(IP) injection of hydro-alcoholic extract of Solanum Melongena were assessed and compared with different doses of morphine and distilled water in Syrian mice. Methods:...

Clinicians in acute care settings are often called upon to manage cancer pain unrelieved by medications. Cognitive-behavioral strategies, such as relaxation and imagery, are recommended for cancer pain management; however, there appear to be individual differences in their effects. This pilot study examined variation in pain outcomes achieved with progressive muscle relaxation (PMR) and analgesic imagery interventions among hospitalized patients with cancer pain, and assessed the influence of...

Full Text Available Objective: To establish a proper experimental model of bone cancer pain in rat for acupuncture research, and observe the pain-relieving effect of electroacupuncture (EA and/or Celebrex on bone cancer pain in rats.Methods: The rat model of bone cancer pain was established by percutaneous direct puncture technique and inoculating the rat mammary gland carcinoma cells Walker 256 into tibial medullary cavity directly, and evaluated by detecting the bone tumor growth and mechanical allodynia. The effects of daily EA treatment and/or Celebrex treatment on the rat mechanical allodynia after intratibial Walker 256 inoculation was observed in this study.Results: Significant mechanical allodynia in ipsilateral hind paw and tumor growth in proximal end of tibial bone of rats in the untreated group were observed after intratibial Walker 256 inoculation. The mechanical allodynia thresholds in rats that received EA or 5 mg/(kg·d Celebrex treatment showed no significant difference as compared with that of rats in the untreated group. However, the mechanical allodynia thresholds of rats in 10 mg/(kg·d Celebrex group showed significant increase after 22- and 26-day treatment as compared with that in the methyl cellulose (MC group. There was significant difference between rats with EA combined with 5 mg/(kg·d Celebrex treatment and rats in the untreated group after 10-, 18- and 23-day treatment.Conclusion: EA and 5 mg/(kg·d Celebrex have synergistic effect on pain relieving and their combined use may enhance the analgesiceffect on bone cancer pain.

?-TRTX-Hhn1b (HNTX-IV) is a 35-amino acid peptide isolated from the venom of the spider, Ornithoctonus hainana. It inhibits voltage-gated sodium channel Nav1.7, which has been considered as a therapeutic target for pain. The goal of the present study is to elucidate the analgesiceffects of synthetic ?-TRTX-Hhn1b on animal models of pain. The peptide was first synthesized and then successfully refolded/oxidized. The synthetic peptide had the same inhibitory effect on human Nav1.7 current transiently expressed in HEK 293 cells as the native toxin. Furthermore, the analgesic potentials of the synthetic peptide were examined on models of inflammatory pain and neuropathic pain. ?-TRTX-Hhn1b produced an efficient reversal of acute nociceptive pain in the abdominal constriction model, and significantly reduced the pain scores over the 40-min period in the formalin model. The efficiency of ?-TRTX-Hhn1b on both models was equivalent to that of morphine. In the spinal nerve model, the reversal effect of ?-TRTX-Hhn1b on allodynia was longer and higher than mexiletine. These results demonstrated that ?-TRTX-Hhn1b efficiently alleviated acute inflammatory pain and chronic neuropathic pain in animals and provided an attractive template for further clinical analgesic drug design. PMID:25123556

Full Text Available ?-TRTX-Hhn1b (HNTX-IV is a 35-amino acid peptide isolated from the venom of the spider, Ornithoctonus hainana. It inhibits voltage-gated sodium channel Nav1.7, which has been considered as a therapeutic target for pain. The goal of the present study is to elucidate the analgesiceffects of synthetic ?-TRTX-Hhn1b on animal models of pain. The peptide was first synthesized and then successfully refolded/oxidized. The synthetic peptide had the same inhibitory effect on human Nav1.7 current transiently expressed in HEK 293 cells as the native toxin. Furthermore, the analgesic potentials of the synthetic peptide were examined on models of inflammatory pain and neuropathic pain. ?-TRTX-Hhn1b produced an efficient reversal of acute nociceptive pain in the abdominal constriction model, and significantly reduced the pain scores over the 40-min period in the formalin model. The efficiency of ?-TRTX-Hhn1b on both models was equivalent to that of morphine. In the spinal nerve model, the reversal effect of ?-TRTX-Hhn1b on allodynia was longer and higher than mexiletine. These results demonstrated that ?-TRTX-Hhn1b efficiently alleviated acute inflammatory pain and chronic neuropathic pain in animals and provided an attractive template for further clinical analgesic drug design.

Full Text Available The ethanolic root extract of Hippocratea africana (200-600 mg kg-1 was evaluated for analgesic, anti-inflammatory and antipyretic properties. The extract dose dependently inhibited acetic acid-induced writhing, formalin-induced paw licking and thermally -induced pain in mice. The extract also inhibited fresh egg albumin, carrageenin and xylene-induced inflammation in mice. These inhibitions were statistically significant (p<0.05 when compared to control. The roots extracts was also found to reduce pyrexia in rats. The analgesic, anti-inflammatory and antipyretic activities of the extract may be related to its active constituents such as tannins, saponins, steroid and flavonoids.

Full Text Available Knee osteoarthritis is the most common cause of disability among people and it is a common disease of joints that can lead to cartilage damage. In this study the analgesiceffects of a herbal ointment containing cinnamon, ginger, mastic (Saghez and sesame oil is compared with Salicylate ointment in patients suffering from knee osteoarthritis. It was a double-blind randomized controlled trail study. Patients with diagnosed arthritis were involved in the study and they were divided in two groups via block randomization method. For six weeks, twice a day, intervention group applied herbal ointment and control group used Salicylate ointment. The severity of pain, morning stiffness and limited motion were measured using Visual Analog Pain Scale. In order to analyze the trends of these three indexes, repeated measurement test was used. Ninety two participates with the mean age of 52.2 (12.4 years and with the mean disease period of 30.45 (30.3 months were involved in the study. There was no significant difference between two groups regarding the distribution of sex, weight, height, BMI and the duration of illness. No statistical difference was observed between two groups regarding pain relief, morning stiffness and limited motion; nevertheless in repeated measurements during second, forth and sixth weeks in both groups the decreasing trend of these three indexes had been statistically significant (p<0.0001. It seems that using this herbal combination is clinically effective for patients suffering from knee osteoarthritis in order to decrease their pain, morning stiffness and limited motion; its effect is comparable with Salicylate ointment.

Different extracts of Nepeta atlantica Ball and Nepeta tuberosa L. ssp. reticulata (Desf.) Maire contain mainly secondary metabolites with iridoïd lactonic and glucosidic type, also with triterpine lupan type.The aerial part of each species is crushed, then extracted in methanol by cold maceration, called global extracts. The global extracts will be extracted through various solvents: initially by hexane, then by dichloromethane, after that by ethyl acetate and at the end by buthanol. Each one of the obtained extracts will be used for the following trials: i) Tail flick trial on the rat for central morphine-like analgesic activity; ii) Koster trial on the mouse for peripheralanalgesic activity. The evaluation of the central and peripheralanalgesic activities for the pre-cited extracts was realized after optimal doses determination of the global extracts activities for both species.The peripheralanalgesic activity test on the mouse showed that, for 60 mg/kg intra peritoneum (IP), the hexanic, dichloromethanic, ethyl acetate and butanic extracts have a protection power against abdominal cramp respectively around 89.78%, 81.73%, 70.9% et 69.05% for Nepeta atlantica Ball, and around 89.16%, 82.98%, 71.52% et 70.27% for Nepeta tuberosa L. ssp. reticulata.Central morphine-like analgesic activity on the rat showed that, for both spices under 60 mg/kg IP, the central analgesic activity effect is significantly for two extracts only: dichloromethane and ethyl acetate. PMID:18937913

Full Text Available Aqueous extract of combination of stems of Tinospora cordifolia, fruits of Emblica officinalis and rhizomes of Cyperus rotundus has been used as traditional herbal drug in Indian medicine system for treatment of fever, body ache, joint pain and inflammation. The collected botanicals were subject to physiochemical, pharmacognostical & phytochemical screening before animal experiments. After acute toxicity studies, anti-inflammatory effect was assessed using carrageen induced paw oedema test and antipyretic effect using yeast induced pyrexia method. Tail immersion, hot plate and writhings test were used for determining the analgesic properties. Phytochemical analysis revealed the presence of polyphenolic flavonoids, tannin and saponins. Significant anti-inflammatory, antipyretic and analgesic properties were noticed in dose dependant manner after aqueous extract administration especially at 600 mg/kg dose. These test drug activities were sustained and comparable to the standard drugs while exhibiting no acute toxicity. Aqueous extract of test drug possesses significantly high anti-inflammatory, antipyretic and analgesic properties without any acute toxicity possibly due to presence of flavonoids.

Xylazine is an alpha(2)-adrenergic agonist extensively used in veterinary medicine and animal experimentation for producing antinociception, sedation, and muscle relaxation. The nitric oxide (NO) / cGMP / ATP-sensitive K(+) (K(ATP)) channel pathway has been proposed as the action mechanism of peripheral antinociception of several groups of drugs, including opioids and nonsteroidal analgesics. Considering the lack of knowledge regarding the mechanisms involved in xylazine effects, the present study investigated the contribution of K(+) channels on peripheral antinociception induced by xylazine using the rat paw pressure test, in which hyperalgesia was induced by intraplantar injection of prostaglandin E(2). Xylazine administered into the right hind paw elicited a local antinociceptive effect, since only much higher doses produced a systemic effect in the contralateral paw. The peripheral antinociceptive effect induced by xylazine was antagonized by glibenclamide, a specific blocker of K(ATP) channels. In another experiment, tetraethylammonium, a voltage-dependent K(+)-channel blocker, and paxilline and dequalinium, which are selective blockers for the large- and small-conductance Ca(2+)-activated K(+) channels, respectively, were ineffective at blocking xylazine antinociception. These results provide evidence that the peripheral antinociceptive effect of xylazine probably results from K(ATP)-channel activation, while the voltage-dependent K(+) channels, small- and large-conductance Ca(2+)-activated K(+) channels, appear not to be involved in this mechanism. PMID:20019444

Full Text Available The study was conducted to evaluate the effects of romifidine alone (50 Âµg/kg and a combination of romifidine (50 Âµg/kg and ketamine (2.5 mg/kg after intrathecal administration in goats. Ten adult goats of either sex weighing between 15 and 20 kg were randomly placed in 2 groups (groups I and II. The agents were administered at the lumbosacral subarachnoid space. Clinico-physiological parameters such as analgesia, motor incoordination, sedation, salivation, heart rate, respiratory rate, arterial pressure, central venous pressure and rectal temperature were studied. Other haematobiochemical parameters monitored were packed cell volume, haemoglobin, plasma proteins, glucose, urea and creatinine. The onset of analgesia was faster in group II (35.5 Â±6.25 s compared to that of group I (5.2 Â±0.54 min. Analgesia of the tail, perineum, hind limbs, flank and thorax was mild to moderate in group I, but complete analgesia of tail, perineum and hind limbs was recorded in group II. Motor incoordination was mild in group I and severe in group II. Significant reduction in heart rate (more pronounced in group I and respiratory rate (more pronounced in group II, and a significant increase in central venous pressure were recorded in both groups. Mean arterial pressure was reduced in both groups, but more markedly in group I. Sedation, electro-cardiogram, rectal temperature and haemato-biochemical parameters did not show significant differences between the 2 groups. The results of this study indicated a possible synergistic analgesic interaction between intrathecally administered romifidine and ketamine, without causing any marked systemic effects in goats.

Full Text Available The objective of the study was to determine the analgesic and systemic effects of subarachnoid administration of xylazine hydrochloride (XY, lidocaine hydrochloride (LI and their combination (XYLI in goats. Six healthy goats were used in a prospective randomised study. Three treatments were administered to each goat, with 1-week intervals between each treatment. Treatments consisted of 0.1 mg/kg xylazine, 2.5 mg/kg lidocaine and a combination of xylazine 0.05 (mg/kg and lidocaine (1.25 mg/kg. Analgesia, ataxic, sedative, cardiovascular and respiratory effects, and rectal temperature were evaluated before (baseline and at 5, 10, 15, and 30 min after subarachnoid injection, and then at 30-min intervals until loss of analgesia occurred. Lidocaine induced analgesia in 3.1 + 1min (mean + SD, which lasted for 66 + 31 min. Heart and respiratory rates and blood pressure remained unchanged after lidocaine-induced analgesia. Xylazine induced analgesia in 9.5 + 2.6 min and xylazine-lidocaine in 3.2 + 1.2 min. Xylazine-lidocaine-induced analgesia lasted longer (178.3 + 37 min than that induced by xylazine (88.3 + 15 min. The XYLI treatment induced prolonged motor blocking (115 min, more than the XY (80 min and LI (90 min treatments. Both xylazine and xylazine-lidocaine caused significant decreases in the heart and respiratory rates, but not in blood pressure. The combination of xylazine (0.05 mg/kg and lidocaine (1.25 mg/kg can be administered subarachnoidally (between last lumbar vertebra and 1st sacral vertebra to produce prolonged (>2.5 h analgesia of the tail, perineum, hind limbs, flanks and caudodorsal rib areas in goats. Despite the prolonged analgesia, using this combination is desirable for relieving postoperative pain, but it may be a disadvantage due to a motor block when dealing with goats.

Full Text Available SciELO Brazil | Language: English Abstract in english OBJECTIVE: The aim of this prospective, randomized study was to evaluate the hemodynamic and analgesiceffects of ketamine by comparing it with propofol starting at the induction of anesthesia until the end of sternotomy in patients undergoing coronary artery bypass grafting surgery. INTRODUCTION: A [...] nesthetic induction and maintenance may induce myocardial ischemia in patients with coronary artery disease. A primary goal in the anesthesia of patients undergoing coronary artery bypass grafting surgery is both the attenuation of sympathetic responses to noxious stimuli and the prevention of hypotension. METHODS: Thirty patients undergoing coronary artery bypass grafting surgery were randomized to receive either ketamine 2 mg.kg-1 (Group K) or propofol 0.5 mg.kg-1 (Group P) during induction of anesthesia. Patients also received standardized doses of midazolam, fentanyl, and rocuronium in the induction sequence. The duration of anesthesia from induction to skin incision and sternotomy, as well as the supplemental doses of fentanyl and sevoflurane, were recorded. Heart rate, mean arterial pressure, central venous pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index, systemic and pulmonary vascular resistance indices, stroke work index, and left and right ventricular stroke work indices were obtained before induction of anesthesia; one minute after induction; one, three, five, and ten minutes after intubation; one minute after skin incision; and at one minute after sternotomy. RESULTS: There were significant changes in the measured and calculated hemodynamic variables when compared to their values before induction. One minute after induction, mean arterial pressure and the systemic vascular resistance index decreased significantly in group P (p

Full Text Available Aims and Context: The objective of the present study was to evaluate the analgesic and adverse effects of intrathecal clonidine with hyperbaric bupivacaine in spinal anesthesia. Settings and Design : Randomized single blind trial. Methods: 210 ASA I-II pregnant females undergoing emergency cesarean section were randomized in a single-blind fashion to one of the three groups. In group I (n=70 patients received 12.5 mg of 0.5% hyperbaric bupivacaine intrathecally. In group II (n=70 patients received intrathecal mixture of 0.5% hyperbaric bupivacaine (8 mg and clonidine 50 ?g. In group III (n=70 , patients received 0.5% hyperbaric bupivacaine (10 mg intrathecally along with 50 ?g of clonidine. Statistical Analysis Used: Groups were compared using one-way ANOVA with the Bonferroni multiple comparison post hoc test. The proportion of adverse events was compared using the chi-square test (?2 =57.2410. Results: On adding 50 ?g clonidine, we were able to reduce intrathecal dose of bupivacaine for cesarean section to 8 mg. Patients receiving intrathecal clonidine along with bupivacaine had significantly long lasting analgesia with lower bupivacaine dose [246.21±5.15 min. (group II vs 146.0±4.55 min (group I, P=0.021; 95% confidence interval: 238.01-257.40, group II and 134.99-157.0 group I]. Conclusions: Addition of intrathecal clonidine causes some sedation in the postoperative period, but it provides adequate analgesia and motor paralysis at lower dose of bupivacaine. It also significantly prolongs postoperative pain relief.

Opioids alter resting state brain oscillations by multiple and complex factors, which are still to be elucidated. To increase our knowledge, multi-channel electroencephalography (EEG) was subjected to multivariate pattern analysis (MVPA), to identify the most descriptive frequency bands and scalp locations altered by remifentanil in healthy volunteers. Sixty-two channels of resting EEG followed by independent measures of pain scores to heat and bone pain were recorded in 21 healthy males before and during remifentanil infusion in a placebo-controlled, double-blind cross-over study. EEG frequency distributions were extracted by a continuous wavelet transform and normalized into delta, theta, alpha, beta and gamma bands. Alterations relative to pre-treatment responses were calculated for all channels and used as input to the MVPA. Compared to placebo, remifentanil increased the delta band and decreased the theta and alpha band oscillations as a mean over all channels (all P?0.007). The most discriminative channels in these frequency bands were: F1 in delta (83.33%, P=0.0023) and theta bands (95.24%, P<0.0001), and C6 in the alpha band (80.95%, P=0.0054). These alterations were correlated to individual changes in heat pain in the delta (P=0.045), theta (P=0.038) and alpha (P=0.039) bands, and to bone pain in the alpha band (P=0.0092). Hence, MVPA of multi-channel EEG was able to identify frequency bands and corresponding channels most sensitive to altered brain activity during remifentanil treatment. As the EEG alterations were correlated to the analgesiceffect, the approach may prove to be a novel methodology for monitoring individual efficacy to opioids. This article is protected by copyright. All rights reserved.

Full Text Available OBJECTIVE: The aim of this prospective, randomized study was to evaluate the hemodynamic and analgesiceffects of ketamine by comparing it with propofol starting at the induction of anesthesia until the end of sternotomy in patients undergoing coronary artery bypass grafting surgery. INTRODUCTION: Anesthetic induction and maintenance may induce myocardial ischemia in patients with coronary artery disease. A primary goal in the anesthesia of patients undergoing coronary artery bypass grafting surgery is both the attenuation of sympathetic responses to noxious stimuli and the prevention of hypotension. METHODS: Thirty patients undergoing coronary artery bypass grafting surgery were randomized to receive either ketamine 2 mg.kg-1 (Group K or propofol 0.5 mg.kg-1 (Group P during induction of anesthesia. Patients also received standardized doses of midazolam, fentanyl, and rocuronium in the induction sequence. The duration of anesthesia from induction to skin incision and sternotomy, as well as the supplemental doses of fentanyl and sevoflurane, were recorded. Heart rate, mean arterial pressure, central venous pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index, systemic and pulmonary vascular resistance indices, stroke work index, and left and right ventricular stroke work indices were obtained before induction of anesthesia; one minute after induction; one, three, five, and ten minutes after intubation; one minute after skin incision; and at one minute after sternotomy. RESULTS: There were significant changes in the measured and calculated hemodynamic variables when compared to their values before induction. One minute after induction, mean arterial pressure and the systemic vascular resistance index decreased significantly in group P (p<0.01. CONCLUSION: There were no differences between groups in the consumption of sevoflurane or in the use of additional fentanyl. The combination of ketamine, midazolam, and fentanyl for the induction of anesthesia provided better hemodynamic stability during induction and until the end of sternotomy in patients undergoing coronary artery bypass grafting surgery.

Full Text Available There is some evidence supporting the reduced activity of integrins following chronic administration of morphine. This reduction might play a role in morphine tolerance development. Manganese binds to the extracellular domain of integrins and makes them to be activated. The effect of integrins activation using manganese on tolerance development to the analgesiceffect of morphine was investigated in this study. Methods: To induce tolerance to analgesiceffect of morphine, morphine (15 ?g/rat was injected intrathecally (i.t. to male adult Wistar rats twice a day for five days. To investigate the effect of manganese, it was injected (20 nmol/rat-i.t. 15 minutes prior to morphine injections during mentioned period. The analgesiceffect of morphine (15 ?g/rat was measured using tail flick test on day 6. Results: The results indicated that in animals which received both manganese and morphine during first 5 days, morphine induced a significant analgesia on day 6. Chronic administration of manganese did not change the pain threshold and morphine induced analgesia. Comparison of morphine analgesia following a single dose of morphine (15 ?g/rat or chronic manganese+morphine, indicated that manganese did not have any effect on the morphine analgesia. Conclusion: Our results showed that, manganese administration prior to morphine is able to prevent morphine tolerance development. It seems that decreased activity of integrins following chronic administration of morphine plays a pivotal role in tolerance development to morphine analgesia. Further investigation needs to determine whether manganese effect is dependent on the integrins role in cell adhesions, or on their intracellular signaling pathways.

Full Text Available Background: Magnesium Sulfate (MgSO4 has been used as a pharmacologic agent in different situations for many years in the treatment of tachyarrhythmias, myocardial ischemia, preeclampsia, and tocolysis among others. The analgesiceffect of MgSO4 for postoperative pain has been used since the 1990s. Postoperative pain is one of the most common complications in the perioperative period and can result in serious consequences in different organs if left untreated. Inguinal herniorrhaphy is among the most common surgeries and is almost always accompanied by severe pain. The object of this study is to determine the effect of a pre-induction infusion of MgSO4 on the reduction of postsurgical pain after herniorrhaphy. Methods: This double-blind, randomized clinical trial included 105 ASA class I and class II herniorrhaphy patients at Shariati Hospital in years 2004 and 2005. For statistical analysis, the ?2 and T tests were used. The patients were divided into three groups based on block randomization. Patients in the following groups received: Group A, 200 ml of normal saline infusion (placebo; Group B, 25 mg/kg MgSO4 in 200 ml of normal saline; Group C, 50 mg/kg MgSO4 in 200 ml of normal saline. All groups were infused twenty minutes before induction of anesthesia using identical methods and dosage in all three groups. Heart rate and mean arterial pressure (MAP at pre- and postintubation and so at skin incision time were charted. Visual analog scale (VAS pain score, nausea, vomiting and the amount of morphine used before recovery room discharge and in six, twelve and twenty-four hours after recovery discharge was recorded. Results: The average age for the different groups was as follows: Group A: 33.6, Group B: 37.37, Group C: 32.74. Nausea and vomiting between the case and control groups were not statistically different (60% vs. 71.4%, p=0.0499, nor was the amount of Morphine used. On recovery room discharge, the VAS scores were 8.1, 7.2, and 5.5 for the first, second and third groups, respectively (P<0.001. However, no statistical significance was found for the VAS scores six hours after recovery room discharge. Conclusion: The results in this study show that pre-induction with MgSO4 has no remarkable effect on decreasing postoperative pain or morphine use for inguinal herniorrhaphy.

Full Text Available Intra- and post-operative analgesiceffects of pre-operative administration of carprofen were investigated in 16 medetomidine-premedicated dogs undergoing elective ovariectomy. Dogs were randomly allocated into carprofen (n=8; 4 mg/kg, intramuscularly or placebo group (n = 8. After medetomidine (1000 [xg/m2, intramuscularly premedication, they were induced with propofol (1 mg/kg, intravenously and maintained with isoflurane (FE'ISO 1.0 % in 100% oxygen. During anaesthesia, the analgesia was assessed in terms of changes in heart rate, respiratory rate and arterial blood pressure as a response to the surgery. Assessments of post-operative sedation (simple numerical rating scale and pain (multifactorial pain scale were made at 15 minutes, 30 minutes, 1,2,3, 4, 5, and 6 hours after the surgery. In addition, pulse rate, respiratory rate and body temperature were measured at the same time. During anaesthesia, lower heart rate, respiratory rate and mean arterial blood pressure and higher tidal volume of respiration were observed in the carprofen group. Post-operative pain score was relatively low in both groups of dogs, however it was higher, but not significantly, in the placebo group. There was no difference between the groups in terms of respiratory and pulse rate after surgery. The post-operative sedation score was higher in the placebo group only in the early post-operative period most probably due to misinterpretation of pain behaviour. Carprofen together with other anaesthetic drugs provided sufficient intra-operative analgesia only until major painful surgical stimulus occurred, after which analgesia had to be supplemented with a subanaesthetic dose of ketamine. Comparing to that analgesia was insufficient in the placebo group throughout the procedure. The post-operative pain scoring system was probably not sensitive enough to detect the differences between the groups; however, the effects of other drugs that extended in the post-operative period may be responsible for a low post­operative pain score in both groups of dogs.

Full Text Available The purpose of this investigation was to study the anti-inflammatory and analgesic properties of total extract and four fractions (ether, ethyl acetate, n-butanol and water from Phlomis lanceolata (Lamiaceae in mice. The plant material was extracted with methanol. In order to estimate the polarity of the active compounds, the total extract was dissolved in water and the water soluble portion was successively partitioned between ether, ethyl acetate and n-buthanol. The total extract and four fractions were analyzed by Thin Layer Chromatography (TLC by use of specific reagents. Dose of 100 mg kg 1 of each extracts were used in carrageenan-induced paw edema, formalin and writhing nociception tests in mice. All compounds reduced paw edema in comparison to the control group at 1, 3, 5 and 7 h post carrageenan injection. The total, ether and aqueous extracts were similar to indomethacin while the ethyl acetate extract was weaker than indomethacin in reduction of paw edema. All extracts induced antinociception in both phases of formalin test. The total and ether extracts were as potent as indomethacin in both phases of formalin test. The ethyl acetate extract was weaker than indomethacin in the second phase of formalin-test while the n-butanol and aqueous extracts showed more antinociception than indomethacin in the second phase of formalin test. All extracts as well as indomethacin induced antinociception in writhing test in comparison to control. The total and aqueous extracts induced the same antinociception as indomethacin while ether, ethyl acetate and n-butanol showed weaker antinociception than indomethacin. Positive results for iridoids and phenolic compounds were indicated by phytochemical analysis of total extract. Phenolic compounds were found in four fractions whereas only n-butanol and aqueous fractions showed positive results for iridoid glycosides. The higher antinociceptive effects of n-butanol and aqueous extracts in the inflammatory phase of formalin test among different extracts tested, might back to the presence of iridoid glycosides, phenolic glycosides or other glycosides. These data suggest that different extracts of P. lanceolata produce different antinociceptive activities that could be due to the effect of one or a combination of the bioactive components in each extract.

Full Text Available SciELO Brazil | Language: English Abstract in english PURPOSE: To measure the change in the minimum alveolar concentration of isoflurane (EtISO) associated with epidural nalbuphine and the postoperative analgesic requirements in dogs after ovariohysterectomy. METHODS: Twenty four healthy female dogs were randomly assigned to receive saline or nal [...] buphine at 0.3 or 0.6 mg/kg (n=8 for each group) administered via lumbosacral epidural catheter introduced cranially into the epidural canal. Changes in heart and respiratory rates and arterial blood pressure during surgery were recorded along with the corresponding EtISO. Immediately after tracheal extubation, analgesia, sedation, heart rate, respiratory rate, and arterial blood pressure were measured at predetermined intervals and every 60 min thereafter until the first rescue analgesic. RESULTS: A significant decrease in EtISO was associated with epidural nalbuphine at 0.3 mg/kg (26.3%) and 0.6 mg/kg (38.4%) but not with saline in ovariohysterectomized dogs. In the postoperative period, VAS and Colorado analgesic scores were lower for the dogs that received the higher nalbuphine dose, which only required supplemental analgesia 10 h following its administration, compared with dogs that received the lower dose. CONCLUSION: Epidural nalbuphine significantly reduces the intra-operative isoflurane requirement and provides prolonged postoperative analgesia after ovariohysterectomy in dogs.

Full Text Available Abstract Background The polypeptide hormone calcitonin is clinically well known for its ability to relieve neuropathic pain such as spinal canal stenosis, diabetic neuropathy and complex regional pain syndrome. Mechanisms for its analgesiceffect, however, remain unclear. Here we investigated the mechanism of anti-hyperalgesic action of calcitonin in a neuropathic pain model in rats. Results Subcutaneous injection of elcatonin, a synthetic derivative of eel calcitonin, relieved hyperalgesia induced by chronic constriction injury (CCI. Real-time reverse transcriptase-polymerase chain reaction analysis revealed that the CCI provoked the upregulation of tetrodotoxin (TTX-sensitive Nav.1.3 mRNA and downregulation of TTX-resistant Nav1.8 and Nav1.9 mRNA on the ipsilateral dorsal root ganglion (DRG, which would consequently increase the excitability of peripheral nerves. These changes were reversed by elcatonin. In addition, the gene expression of the calcitonin receptor and binding site of 125I-calcitonin was increased at the constricted peripheral nerve tissue but not at the DRG. The anti-hyperalgesic effect and normalization of sodium channel mRNA by elcatonin was parallel to the change of the calcitonin receptor expression. Elcatonin, however, did not affect the sensitivity of nociception or gene expression of sodium channel, while it suppressed calcitonin receptor mRNA under normal conditions. Conclusions These results suggest that the anti-hyperalgesic action of calcitonin on CCI rats could be attributable to the normalization of the sodium channel expression, which might be exerted by an unknown signal produced at the peripheral nerve tissue but not by DRG neurons through the activation of the calcitonin receptor. Calcitonin signals were silent in the normal condition and nerve injury may be one of triggers for conversion of a silent to an active signal.

Circadian variation in biological rhythms has been identified as affecting both labour pain and the pharmacological properties of analgesics. In the context of pain, there is also a growing body of evidence suggesting the importance of adult attachment. The purpose of this study was to examine whether labour pain, analgesic consumption and pharmacological effect are significantly affected by the time of day and to analyse whether this circadian variation is influenced by women's attachment style. This prospective observational study included a sample of 81 pregnant women receiving patient-controlled epidural analgesia (PCEA). Attachment was assessed with the Adult Attachment Scale - Revised. The perceived intensity of labour pain in the early stage of labour (3?cm of cervical dilatation and before the administration of PCEA) was measured using a visual analogue scale (VAS). Pain was also indirectly assessed by measuring the consumption of anaesthetics. The latency period and the duration of effect were recorded for a chronopharmacology characterisation. Pain, as assessed with the VAS, was significantly higher in the night-time group than in the daytime group. An insecure attachment style was significantly associated with greater labour pain at 3?cm of cervical dilatation (p?style was not significant for any of the study variables. Our results provide evidence of the importance of circadian variation in studying labour pain and the pharmacological effect of labour analgesia involving epidural blockage with a PCEA regimen. Moreover, although there was no evidence that attachment style influenced the circadian variation, these data emphasise that insecure attachment patterns are a risk factor for greater labour pain and analgesic consumption, which should be considered in pain management approaches. PMID:24673295

The hematotoxic effects of benzene exposure may be important in the occurrence of subsequent health effects. We sought to provide further information on peripheral blood effects by studying 928 workers in five factories in and around Shanghai, China exposed to a wide range of benzene concentrations. Specifically, we sought to investigate which blood indices are more strongly related to benzene exposure and which concentration levels of benzene result in peripheral blood changes. Lifestyle habits and demographic information was obtained via questionnaire, and potentially important genetic influences were determined by assessing single nucleotide polymorphisms in four genes (NQO1, MPO, CYP2E1, GSTT1). Weekly benzene exposure estimated from individual monitoring results ranged from 0.07 to 872 mg/m(3) with a median value of 7.4 mg/m(3). Twelve peripheral blood indices were examined. Stronger effects on peripheral blood were seen for red cell indices such as anemia and macrocytosis, albeit at higher (>10 ppm) exposure levels. The most sensitive parameters to benzene appeared to be neutrophils and the mean platelet volume (MPV), where effects were seen for benzene air concentrations of 7.8-8.2 ppm. Toluene exposure is a potential confounder for some peripheral blood effects, pointing to the need to scrutinize levels of both compounds in the occupational environment. PMID:20034484

Background Studies have shown that N-methyl-D-aspartate receptor (NMIDA) plays an essential role in postoperative pain. It seems that use of NMDA receptor antagonists such as Dextromethorphan intensifies the analgesiceffects of opioids. Objectives In this study, we evaluated the effect of preoperative administration of Dextromethorphan on postoperative pain reduction. Patients and Methods This double blind randomized clinical trial was conducted on arthroscopic surgery candidates. Participants were randomly allocated to interventions and assigned to two groups of Dextromethorphan and placebo. In Dextromethorphan group, the patients received 1 mg/kg Dextromethorphan orally the night before the operation. Pain severity based on the visual analog scale (VAS) up to 16 hours postoperation, use of opioids, and the first request for analgesics were recorded postoperatively. Results A total of 112 patients in the Dextromethorphan (n = 54) and placebo groups (n = 58) were evaluated. No significant difference was detected between the two groups for age, sex or ASA. The mean amount of opioid consumption was significantly lower in patients who received Dextromethorphan (10.7 ± 5.6 mg) compared to the placebo group (13.1 ± 5.6 mg), (P = 0.03). The mean time until the first opioid request in patients who received Dextromethorphan was longer than that in the placebo group (P = 0.01). Conclusions The study results demonstrated that preemptive use of Dextromethorphan reduced postoperative pain and opioid consumption. PMID:24660143

The fruit of Terminalia chebula Retzius has been used as a panacea in India and Southeast Asia but its biological activities have not been fully elucidated. Here we report anti-arthritic and analgesiceffect of NDI10218, a standardized ethanol extract of Terminalia chebula, on collagen-induced arthritis and acetic acid-induced writhing model, respectively. Arthritis was induced in DBA/1J mice by immunizing bovine type II collagen and mice were treated with NDI10218 daily for 5 weeks after the onset of the disease. NDI10218 reduced the arthritis index and blocked the synovial hyperplasia in a dose-dependent manner. The serum levels of pro-inflammatory cytokines TNF-?, IL-6, and IL-1? were significantly reduced in mice treated with NDI10218. Production of the inflammatory IL-17, but not immunosuppressive IL-10, was also inhibited in splenocytes isolated from NDI10218-treated arthritis mice. Administration of NDI10218 markedly decreased the number of T cell subpopulations in the regional lymph nodes of the arthritis mice. Finally, NDI10218 reduced the number of abdominal contractions in acetic acid-induced writhing model, suggesting an analgesiceffect of this extract. Taken together, these results suggest that NDI10218 can be a new therapeutic candidate for the treatment of rheuma-toid arthritis. PMID:24116282

The analgesic activity of a single dose of lamotrigine (300 mg p.o.) and phenytoin (300 mg p.o.) was evaluated in a randomised, double-blind, placebo-controlled study in 12 healthy volunteers. A computerised cold-pressor test (CPT) was used to measure analgesia. Dihydrocodeine (90 mg p.o.) was used to validate the effectiveness of the CPT in measuring analgesia in the volunteers. On each study day the volunteers performed the CPT before study medication and at 1.25, 2.75, 4.25 and 5.75 h post-dose. Psychomotor tests were carried out before each CPT to determine possible drug-induced sedation. These included digit symbol substitution, critical flicker fusion and choice reaction time. Subjective feelings of concentration, vigilance and relaxation were also measured using visual analogue scales. All three active drugs significantly reduced pain scores. Maximum pain relief was achieved at 1.25 h post-dose for both dihydrocodeine and lamotrigine, whereas for phenytoin it occurred at 4.25 h post-dose. There was a significant association between analgesia and plasma concentrations of lamotrigine (P = 0.013) and phenytoin (P = 0.028). There were no significant differences in the sedation produced by any of the active drugs, compared to placebo. The findings of this study suggest that lamotrigine and phenytoin could have a wider clinical use as analgesics. PMID:9718254

Using a modelling approach, this study aimed to (i) examine whether the pharmacodynamics of the analgesic and anti-hyperalgesic effects of morphine differ; (ii) investigate the influence of demographic, pain sensitivity and genetic (OPRM1) variables on between-subject variability of morphine pharmacokinetics and pharmacodynamics in human experimental pain models. The study was a randomized, double-blind, 5-arm, cross-over, placebo-controlled study. The psychophysical cutaneous pain tests, electrical pain tolerance (EPTo) and secondary hyperalgesia areas (2HA) were studied in 28 healthy subjects (15 males). The subjects were chosen based on a previous trial where 100 subjects rated (VAS) their pain during a heat injury (47°C, 7 min., 12.5 cm(2) ). The 33% lowest- and highest pain sensitive subjects were offered participation in the present study. A two-compartment linear model with allometric scaling for weight provided the best description of the plasma concentration-time profile of morphine. Changes in the EPTo and 2HA responses with time during the placebo treatment were best described by a linear model and a quadratic model, respectively. The model discrimination process showed clear evidence for adding between occasion variability (BOV) on baseline and the placebo slope for EPTo and 2HA, respectively. The sensitivity covariate was significant on baseline EPTo values, and genetics as a covariate on the placebo slope for 2HA. The analgesic and anti-hyperalgesic effects of morphine were pharmacologically distinct as the models had different effect site equilibration half-lives and different covariate effects. Morphine had negligible effect on 2HA, but significant effect on EPTo. This article is protected by copyright. All rights reserved.

The ?-conotoxin ?-KIIIA, from Conus kinoshitai, blocks mammalian neuronal voltage-gated sodium channels (VGSCs) and is a potent analgesic following systemic administration in mice. We have determined its solution structure using NMR spectroscopy. Key residues identified previously as being important for activity against VGSCs (Lys7, Trp8, Arg10, Asp11, His12 and Arg14) all reside on an ?-helix with the exception of Arg14. To further probe structure-activity relationships of this toxin against VGSC subtypes, we have characterised the analogue ?-KIIIA[C1A,C9A], in which the Cys residues involved in one of the three disulfides in ?-KIIIA were replaced with Ala. Its structure is quite similar to that of ?-KIIIA, indicating that the Cys1-Cys9 disulfide bond could be removed without any significant distortion of the ?-helix bearing the key residues. Consistent with this, ?-KIIIA[C1A,C9A] retained activity against VGSCs, with its rank order of potency being essentially the same as that of ?-KIIIA, namely, NaV1.2 > NaV1.4 > NaV1.7 ? NaV1.1 > NaV1.3 > NaV1.5. Kinetics of block were obtained for NaV1.2, NaV1.4 and NaV1.7, and in each case both kon and koff values of ?-KIIIA[C1A,C9A] were larger than those of ?-KIIIA. Our results show that the key residues for VGSC binding lie mostly on an ?-helix and that the first disulfide bond can be removed without significantly affecting the structure of this helix, although the modification accelerates the on- and off-rates of the peptide against all tested VGSC subtypes. These findings lay the groundwork for the design of minimized peptides and helical mimetics as novel analgesics. PMID:19170536

Over the recent years compelling evidence has accumulated indicating that botulinum neurotoxin serotype A (BoNT/A) results in analgesiceffects on neuropathic as well as inflammatory pain, both in humans and in animal models. In the present study, the pharmacological interaction of BoNT/A with morphine in fighting inflammatory pain was investigated in mice using the formalin test. Moreover, the effects of BoNT/A on the tolerance-induced by chronic administration of morphine were tested and the behavioral effects were correlated with immunofluorescence staining of glial fibrillary acidic protein, the specific marker of astrocytes, at the spinal cord level. An ineffective dose of BoNT/A (2 pg/paw) combined with an ineffective dose of morphine (1 mg/kg) exerted a significant analgesic action both during the early and the late phases of formalin test. A single intraplantar injection of BoNT/A (15 pg/paw; i.pl.), administered the day before the beginning of chronic morphine treatment (7 days of s.c. injections of 20 mg/kg), was able to counteract the occurrence of tolerance to morphine. Moreover, BoNT/A reduces the enhancement of the expression of astrocytes induced by inflammatory formalin pain. Side effects of opiates, including the development of tolerance during repeated use, may limit their therapeutic use, the possibility of using BoNT/A for lowering the effective dose of morphine and preventing the development of opioid tolerance would have relevant implications in terms of potential therapeutic perspectives. PMID:22281280

In a double-blind study, 2 mg of morphine in saline, or saline only, was given subcutaneously into a second-degree bilateral leg-burn injury in 12 volunteers. Heat-pain thresholds and pressure-pain thresholds were significantly increased by local morphine administration. These results confirm experimental data demonstrating a peripheral antinociceptive effects of opioids in inflamed tissue.

Myrica rubra Sieb. et Zucc. leaves are commonly used as an astringent, antidiarrheic, and analgesics in folk medicine in China. In the present study, the analgesic activity of myricetin, a major compound in Myrica rubra Sieb. et Zucc. leaves was evaluated in vivo. The analgesiceffect of myricetin was tested by a serial of models, such as acetic acid-induced writhing response, formalin-induced paw licking and hot plate test. The sedative activity was evaluated by pentobarbital-induced sleep time. Platelet aggregation induced by collagen and arachidonic acid was also performed in vitro. Myricetin showed a significant inhibition on chemical nociceptive models such as the acetic acid-induced writhing response and the licking time on the late phase in the formalin test in a dose-dependent manner, but did not manifest a signicant effect in hot plate test. Myricetin was also not able to increase the sleeping time induced by pentobarbital, which further indicated that the analgesiceffect of myricetin was unrelated to sedation. In addition, myricetin inhibited the content of PGE2 in the peritoneal fluid and platelet aggregation induced by collagen and arachidonic acid in vitro. These results collectively demonstrated that myricetin possessed potent analgesic activity, which was related with peripheral analgesia, but, not with the opioid system. Myricetin may be a potent COX-1 inhibitor with anti-platelet activity. PMID:19407970

Two recent developments of opioid peptide-based analgesics are reviewed. The first part of the review discusses the dermorphin-derived, cationic-aromatic tetrapeptide H-Dmt-D-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA, where Dmt indicates 2',6'-dimethyltyrosine), which showed subnanomolar mu receptor binding affinity, extraordinary mu receptor selectivity, and high mu agonist potency in vitro. In vivo, [Dmt(1)]DALDA looked promising as a spinal analgesic because of its extraordinary antinociceptive effect (3000 times more potent than morphine) in the mouse tail-flick assay, long duration of action (4 times longer than morphine), and lack of effect on respiration. Unexpectedly, [Dmt(1)]DALDA also turned out to be a potent and long-acting analgesic in the tail-flick test when given subcutaneously (s.c.), indicating that it is capable of crossing the blood-brain barrier. Furthermore, little or no cross-tolerance was observed with s.c. [Dmt(1)]DALDA in morphine-tolerant mice. The second part of the review concerns the development of mixed mu agonist/delta antagonists that, on the basis of much evidence, are expected to be analgesics with a low propensity to produce tolerance and physical dependence. The prototype pseudopeptide H-Dmt-TicPsi[CH(2)NH]Phe-Phe-NH(2) (DIPP-NH(2)[Psi], where Tic indicates 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) showed subnanomolar mu and delta receptor binding affinities and the desired mu agonist/delta antagonist profile in vitro. DIPP-NH(2)[Psi] produced a potent analgesiceffect after intracerebroventricular administration in the rat tail-flick assay, no physical dependence, and less tolerance than morphine. The results obtained with DIPP-NH(2)[Psi] indicate that mixed mu agonist/delta antagonists look promising as analgesic drug candidates, but compounds with this profile that are systemically active still need to be developed. PMID:16353933

Full Text Available The analgesiceffect of the centrally acting opioid, tramadol, is well-known. It has been shown in clinical studies that using tramadol epidurally can provide longer duration of analgesia, without the common side effects of opioids. The study was undertaken to evaluate the duration of analgesia and/or pain free period produced by intrathecal tramadol added to bupivacaine in patients undergoing major gynecological surgery in a randomized double blind placebo controlled protocol. Fifty patients ASA I & II scheduled for Wardmayo?s operation and Fothergill?s operation were randomly allocated to two equal groups. Group A (n=25 received 3 ml of 0.5% hyperbaric bupivacaine (15 mg with 0.2 ml of normal saline and Group B (n=25 received 3 ml 0.5% hyperbaric bupivacaine and 0.2 ml (20 mg tramadol by intrathecal route at L3-4 inter space. Standard monitoring of the vital parameters was done during the study period. Levels of sensory block and sedation score were recorded every two minutes for the first 20 minutes, and then every ten minutes for the rest of the surgical procedure. Assessment of pain was done using Visual Analogue Scale (VAS. The study was concluded when the VAS was more than 40 mm, postoperatively. The patient was medicated and the time was recorded. Duration of analgesia or pain free period was estimated from the time of completion of spinal injection to administration of rescue analgesic or when the VAS score was greater than 40 mm. In Group B patients, the VAS score was significantly lower, as compared to Group A patients. The duration of analgesia was 210 ± 10.12 min in Group A; whereas, in Group B, it was 380 ± 11.82 min, which was found to be significant.

Full Text Available In the present investigation a comparative analysis of the Free radical scavenging potential and analgesic activity of the Ethanolic Leaf (ELS and stem extracts (ESS of Solanum nigrum was performed. The extracts were evaluated for its DPPH and hydroxyl free radicals scavenging effect and inhibitory potential on protein carbonyl formation. Total phenolic and flavonoid content of the extracts were also determined by a colorimetric method. The ethanolic extracts of Solanum nigrum were evaluated for its peripheralanalgesic activity by Acetic-acid induced writhing response and central analgesic activity by Tail flicking method and Hot plate method in mice. Both the plant extracts scavenged the free radicals in a dose dependent manner. However the scavenging effect was more pronounced in ELS extract when comparable to ESS extract. Both the extract possessed considerable quantity of phenols and flavonoids. In Tail flicking and Hot plate methods the ELS extract of Solanum nigrum showed higher mean basal latency time when comparable to ESS extract suggesting its central analgesic activity. Similarly in Acetic acid induced writhing response the ELS extract exhibited a significant inhibition of writhing 53.28% when comparable to ESS which exhibited an inhibition of 46.53%. The positive control Diclofenac sodium showed 70.66% of writhing inhibition. The analgesic activity of the plants extracts is probably due to its free radical scavenging activity.

Full Text Available Objective. To evaluate the pharmacological, clinical and toxicological effects of celecoxib and meloxicam for analgesia for 30 days in dogs with hip osteoarthritis. Materials and methods. Twenty-four patients were evaluated, 75% were females with an average age of 7.16 ± 2.06 years and twenty five percent were males with an average age of 7.83 ± 2.22 years. All patients had hip osteoarthritis and they were randomized into two groups; one group received oral celecoxib 5 mg/kg every 12 hours during one month and the second group received oral meloxicam 0.2 mg/kg every 24 hours during 1 month. The patients were evaluated for analgesia, and hematological, renal, liver, and coagulation tests on days 0, 10th and 30th after treatment initiation, and a gastric endoscopy on day 30. Statistical analysis was performed using a HSD Tukey test and c2 with a 5% level of statistical significance. Results. Both drugs reduced articular pain according to the Melbourne scale during the 30 days of treatment (p?0.05. Hematological, renal, hepatic and coagulation tests were normal in both treatment groups. All patients presented chronic gastritis on endoscopy on day 30th. Conclusions. Both drugs decreased pain at day 30th without causing alterations in hematological, renal, hepatic or coagulation tests after 30 days of treatment. However, both drugs induced chronic gastritis.

Full Text Available The leaves of Mitragyna speciosa Korth. (M. speciosa were extracted with methanol to give methanol extract. The methanol extract was made in acid and then in alkaline and extracted with chloroform to give alkaloid extract. The effects of the methanol and alkaloid extracts on analgesic activities in hot plate test in mice and tail flick test in rats and behavioral activities in locomotor activity and pentobarbital-induced sleep in mice, were examined. In acute toxicity test, the LD50 values of oral administration of the methanol and alkaloid extracts of M. speciosa leaves in mice were 4.90 g/kg and 173.20 mg/kg, respectively. Oral administration (50, 100 and 200 mg/kg of the methanol extract of M. speciosa leaves significantly prolonged the latency of nociceptive response on hot plate test in mice. The alkaloid extract of M. speciosa also increased the pain response latency at the dose of 20 mg/kg but less potent than those of the methanol extract (100 mg/kg in mice (comparing 5-10 mg/kg alkaloid extract with corresponding to approximately 200 mg/kg of methanol extract. The antinociceptive action of either methanol extract (100 mg/kg, p.o. or alkaloid extract (20 mg/kg, p.o. of M. speciosa leaves was blocked by naloxone (2 mg/kg, i.p. in mice. Neither the methanol extract nor the alkaloid extract significantly prolonged latency of nociceptive response on tail flick test in rats. Both of the extracts had no significant change on spontaneous motor activity or pentobarbital-induced sleep in mice, respectively. These results suggest that the methanol and alkaloid extracts of M. speciosa leaves possess the analgesic activity which partly acted at opioid receptors in the supraspinal opioid system.

Full Text Available Opiate and opioid analgesics are important drugs in the treatment of pain. They are associated with addiction and respiratory depression, side effects which limit their clinical usefulness. This paper describes the main classes of agonists and antagonists to opioid receptors (D, G, N. The main drugs will be shown emphasizing the structure-activity relationship, as well as biotransformation reactions.

Full Text Available Abstract Background Electrical acupuncture (EA has been utilized in acute pain management. However, the neuronal mechanisms that lead to the analgesiceffect are still not well defined. The current study assessed the intensity [optimal EA (OI-EA vs. minimal EA (MI-EA] effect of non-noxious EA on supraspinal regions related to noxious heat pain (HP stimulation utilizing an EA treatment protocol for acute pain and functional magnetic resonance imaging (fMRI with correlation in behavioral changes. Subjects underwent five fMRI scanning paradigms: one with heat pain (HP, two with OI-EA and MI-EA, and two with OI-EA and HP, and MI-EA and HP. Results While HP resulted in activations (excitatory effect in supraspinal areas known for pain processing and perception, EA paradigms primarily resulted in deactivations (suppressive effect in most of these corresponding areas. In addition, OI-EA resulted in a more robust supraspinal sedative effect in comparison to MI-EA. As a result, OI-EA is more effective than MI-EA in suppressing the excitatory effect of HP in supraspinal areas related to both pain processing and perception. Conclusion Intensities of EA plays an important role in modulating central pain perception.

Background Electrical acupuncture (EA) has been utilized in acute pain management. However, the neuronal mechanisms that lead to the analgesiceffect are still not well defined. The current study assessed the intensity [optimal EA (OI-EA) vs. minimal EA (MI-EA)] effect of non-noxious EA on supraspinal regions related to noxious heat pain (HP) stimulation utilizing an EA treatment protocol for acute pain and functional magnetic resonance imaging (fMRI) with correlation in behavioral changes. Subjects underwent five fMRI scanning paradigms: one with heat pain (HP), two with OI-EA and MI-EA, and two with OI-EA and HP, and MI-EA and HP. Results While HP resulted in activations (excitatory effect) in supraspinal areas known for pain processing and perception, EA paradigms primarily resulted in deactivations (suppressive effect) in most of these corresponding areas. In addition, OI-EA resulted in a more robust supraspinal sedative effect in comparison to MI-EA. As a result, OI-EA is more effective than MI-EA in suppressing the excitatory effect of HP in supraspinal areas related to both pain processing and perception. Conclusion Intensities of EA plays an important role in modulating central pain perception. PMID:21645415

Previous studies have shown a superior analgesiceffect of favorite music over other passive or active distractive tasks. However, it is unclear what mediates this effect. In this study we investigated to which extent distraction, emotional valence and cognitive styles may explain part of the relationship. Forty-eight healthy volunteers received heat stimuli during an active mental arithmetic task (PASAT), and passive listening to music (Mozart), environmental sounds (rain and water), and control (noise). The participants scored the conditions according to affective scales and filled out questionnaires concerning cognitive styles (Baron – Cohen and self-report). Active distraction with PASAT led to significantly less pain intensity and unpleasantness as compared to music and sound. In turn, both music and sound relieved pain significantly more than noise. When music and sound had the same level of valence they relieved pain to a similar degree. The emotional ratings of the conditions were correlated with the amount of pain relief and cognitive styles seemed to influence the analgesia effect. These findings suggest that the pain relieving effect previously seen in relation to music may be at least partly mediated by distraction, emotional factors and cognitive styles rather than by the music itself.

Full Text Available Stephanie Anderson1,2, Hollis Krug1,2, Christopher Dorman1, Pari McGarraugh1, Sandra Frizelle1, Maren Mahowald1,21Rheumatology Section, Veteran’s Affairs Medical Center, Minneapolis, Minnesota; 2Division of Rheumatology and Autoimmune Diseases, University of Minnesota Medical School, Minneapolis, Minnesota, USAObjective: To evaluate the analgesiceffectiveness of intra-articular botulinum toxin Type B (BoNT/B in a murine model of chronic degenerative arthritis pain.Methods and materials: Chronic arthritis was produced in adult C57Bl6 mice by intra-articular injection of Type IV collagenase into the left knee. Following induction of arthritis, the treatment group received intra-articular BoNT/B. Arthritic control groups were treated with intra-articular normal saline or sham injections. Pain behavior testing was performed prior to arthritis, after induction of arthritis, and following treatments. Pain behavior measures included analysis of gait impairment (spontaneous pain behavior and joint tenderness evaluation (evoked pain response. Strength was measured as ability to grasp and cling.Results: Visual gait analysis showed significant impairment of gait in arthritic mice that improved 43% after intra-articular BoNT/B, demonstrating a substantial articular analgesiceffect. Joint tenderness, measured with evoked pain response scores, increased with arthritis induction and decreased 49.5% after intra-articular BoNT/B treatment. No improvement in visual gait scores or decrease in evoked pain response scores were found in the control groups receiving intra-articular normal saline or sham injections. Intra-articular BoNT/B was safe, and no systemic effects or limb weakness was noted.Conclusions: This study is the first report of intra-articular BoNT/B for analgesia in a murine model of arthritis pain. The results of this study validate prior work using intra-articular neurotoxins in murine models. Our findings show chronic degenerative arthritis pain can be quantitated in a murine model by measuring gait impairment using visual gait analysis scores (spontaneous pain behavior and joint tenderness scores (evoked pain responses. Reduction of joint pain seen in this study is consistent with our hypothesis of inhibition of release of pain mediators by intra-articular BoNT/B, supporting further investigation of this novel approach to treatment of arthritis pain with intra-articular neurotoxins.Keywords: intra-articular BoNT/B, osteoarthritis

Full Text Available The Ecbolium linnaenum(leaves is used as a folk medicine in Bangladesh for pain, diarrhea and infectious diseases. Phytochemical evaluation of the ethanolic extracts of Ecboliumlinnaenumleaves demonstratesthese pharmacologic effect for the presence of alkaloids, tannins, gums,flavonoids and absence of carbohydrates, steroids, saponins. In this present study an attempt was made to determine the analgesic, antidiarrhoel, antioxidantand antimicrobial effectin Swiss Albino mice. Ethanolic extracts of250 and 500 mg/kg showed significant inhibition of writhing reflex 36.20% (P< 0.01 and 54.48% (P< 0.001, respectively while the standard drug diclofenac-Na was 75.52% (P< 0.001 at a dose of 25 mg/kg body weight.In the castor oil-induced diarrhoealmice, the ethanolic extracts of 250 mg/kg & 500 mg/kg, raised the latent period and reduced the number of stools comparing with standard drug Loperamide. 0.02% DPPH solution of ethanol on TLC plate showed the presence of anti-oxidant components in the Ecboliumlinnaenum.From the % inhibition of ascorbic acid and Ecboliumlinnaenum we observe that it has anti-oxidation effect. The IC50 (inhibitory conc. 50% for ascorbic acid is approximately 1 µg/ml and for the sample it is more than 500 µg/ml. The ethanolic extract of Ecboliumlinnaenum was tested for antimicrobial activity against a number of both gram positive and gram-negative bacteria but it does not show any anti-microbial effect.

The symptomatic treatment of pain associated with spasm of gastrointestinal or genitourinary origin can include the use of spasmolytic agents and/or non-steroidal anti-inflammatory drugs. However, the evidence of a superior effectiveness of combination in comparison with individual drugs is scarce and controversial. A double-blind, randomised, clinical trial study was designed to characterize the analgesiceffect and safety of ketorolac and hyoscine butylbromide against hyoscine butylbromide alone in patients with ambulatory acute cramping pain of gastrointestinal and genitourinary origin. 160 patients with a pain level ?4 in a 1-10?cm visual analogue scale were allocated to receive a fixed dose of ketorolac/hyoscine butylbromide (10?mg/20?mg) or hyoscine butylbromide (20?mg) alone at 6?h intervals, during a 48?h period. Both treatments were similarly effective when compared as a whole or when groups were classified by pain origin. Conversely, when treatments were grouped by pain intensity, ketorolac/hyoscine butylbromide combination showed a significant better pain relief profile than hyoscine butylbromide alone in pain intensity ?7, but not ketorolac/hyoscine butylbromide mixture could be a better option than hyoscine butylbromide alone in the treatment of some acute intense cramping painful conditions. PMID:23093479

Full Text Available Introduction: Nowadays, many researches are being conducted in order to evaluate the analgesiceffects of different plants which have been used as sedative in traditional medicine. Solanum Melongena is a plant with different theories about its analgesiceffects. In this experimental trial research, the effects of intraperitoneal(IP injection of hydro-alcoholic extract of Solanum Melongena were assessed and compared with different doses of morphine and distilled water in Syrian mice. Methods: The effects of different doses of Solanum Melongena (1, 10, 100, and 1000µg/Kg, different doses of morphine sulfate (1, 2, and 4 µg/Kg and distilled water on acute pain was assessed in Syrian mice. Tail flick latency after IP injection was measured for 75 minutes as the index of pain tolerance, using a tail flick apparatus which projects a condensed light stimulus on the animal's tail. Results: Our findings showed that different doses of Solanum increased analgesia index. This effect was more prominent in 45-60 minutes after IP injections which was significantly greater than the control group (p<0.05(. Conclusion: Our findings indicated that the hydro-alcoholic extract of Solanum Melongena produces analgesiceffect in a dose- related manner.

SUMMARY Dexketoprofen trometamol is the dextrorotary enantiomer of the NSAID ketoprofen formulated as a tromethamine salt. The purpose of administering 50% of the racemic mixture is to keep the same analgesic and anti-inflammatory effect while reducing the adverse events due to both enantiomers. This article describes the pharmacological properties and evaluates the analgesiceffects of dexketoprofen trometamol reported in acute and chronic pain conditions. The main conclusions are that dexketoprofen trometamol appears as effective as the double dose of the racemic drug. However, the reduction of adverse effects still has to be demonstrated. In addition, the formulation as tromethamine salt appears beneficial regarding fast onset of analgesia in acute pain conditions. PMID:24645708

Kisspeptins are structurally closely related peptides derived from the Kiss1 gene that have been demonstrated to stimulate the hypothalamo-pituitary gonadal axis. The natural peptide products derived from post-translational processing of the kisspeptin precursor have not been elucidated. We examined the acute effect on serum levels of free testosterone in the adult male mouse after systemic administration of kisspeptins with different lengths of both human and mouse origin. Mouse kisspeptin-10 and -52 dose-dependently increased serum testosterone, and both peptides showed similar potency and efficacy. Human kisspeptin-10 and kisspeptin-54 evoked robust increase in serum testosterone, with the same potency as for mouse kisspeptins. Other members of the RFRP family of peptides, i.e. RFRP-1 and -3 were inactive. Time-course experiments revealed that the longer forms had a slower onset of action, and the long human form also a more prolonged effect. The effect of the peripherally administered mouse kisspeptin-10 could be totally blocked by the GnRH antagonist acyline. Finally, peripherally administered mouse kisspeptin-10 had no effect on Fos induction in GnRH cells. These data show that all peptides tested are active and supports the concept that their effect is mediated by a target upstream of the pituitary, such as the median eminence.

In the present study, we investigated the role of 5-hydroxytryptamine type 3 (5-HT(3)) receptors in hypnosis and analgesia induced by emulsified sevoflurane. A mouse model of hypnosis and analgesia was established by an intraperitoneal or subcutaneous injection of emulsified sevoflurane.We intracerebroventricularly (i.c.v.) or intrathecally (i.t.) administered YM-31636, a 5-HT(3) receptor agonist, to mice and observed sleep time during hypnosis. In addition, the tail withdrawal latency was measured using the tail withdrawal test, and the writhing time was determined using the acetic acid writhing test. In the hypnosis test, YM-31636 (5, 10 and 15 ?g, i.c.v.) treatment significantly decreased emulsified sevoflurane-induced mouse sleep time (p YM-31636 (2.5, 5 and 10 ?g, i.t.) treatment significantly and dose-dependently decreased the tail withdrawal latency (p < 0.05 or p < 0.01) and increased the writhing time (p < 0.01) of mice treated with emulsified sevoflurane. These results suggest that 5-HT(3) receptors may modulate the hypnotic and analgesiceffects induced by emulsified sevoflurane. PMID:20885002

The in vitro and in vivo effects of therapeutical doses of acetylsalicylic acid on lymphocyte subpopulations in peripheral blood were investigated with the following results: Acetylsalicylic acid caused both in vitro and in vivo a reduction of complement receptor bearing lymphocytes and of lymphocytes identified with fluorescent rabbit antibody to human Ig (polyvalent) and to human IgG. Sheep red blood cell receptor bearing lymphocytes, and lymphocytes identified with antibody to human IgM and IgD were unaffected by acetylsalicylic acid.

Abstract Background We have previously reported that inhibition of astrocytic activation contributes to the analgesiceffects of intrathecal ketamine on spinal nerve ligation (SNL)-induced neuropathic pain. However, the underlying mechanisms are still unclear. c-Jun N-terminal kinase (JNK), a member of mitogen-activated protein kinase (MAPK) family, has been reported to be critical for spinal astrocytic activation and neuropathic pain development after SNL. Ketamine can decre...

BACKGROUND: The pharmacokinetics and clinical efficacy of ropivacaine (2.5 mg/ml) during a 24-h continuous epidural infusion for postoperative pain relief in 20 patients scheduled for abdominal hysterectomy were characterized using an open-label, increasing-dose design. METHODS: Through an epidural catheter inserted at T10-T12, a test dose of 7.5 mg ropivacaine was given 3 min before a bolus dose of 42.5 mg and immediately followed by a 24-h continuous epidural infusion with either 10 or 20 mg/h. Peripheral venous plasma samples were collected up to 48 h after infusion, and urinary excretion was followed up to the end of infusion. Postoperative pain at rest, on coughing, and at mobilization was assessed by means of a visual analog scale 2,4,6,8,12, and 24 h after the end of surgery. Sensory (pinprick) and motor block (modified Bromage scale) were assessed at the same intervals. RESULTS: The total plasma concentrations of ropivacaine increased markedly and consistently during the 24-h epidural infusion, in contrast to stable unbound concentrations. Both total and unbound plasma concentrations at the end of infusion were proportional to the total dose, although only the latter was proportional to the infusion rate. The total and unbound plasma clearance was independent of dose. Total mean clearance decreased on average by 21% (P < 0.001) during the last 12 h of epidural infusion, i.e., from 539 +/- 191 ml/min to 418 +/- 138 ml/min, indicating time-dependent kinetics. The unbound clearance also varied between estimates after 8 h of infusion and the end of treatment, i.e., a 5.3% decrease from 10.4 +/- 5.3 l/min to 9.5 +/- 3.9 l/min (P < 0.05). The unbound fraction of ropivacaine in plasma decreased during treatment, and this was related to the increase in alpha1-acid glycoprotein concentration. Pain was generally well controlled, and median visual analog scale scores during mobilization were less than 30 mm in patients receiving ropivacaine at 20 mg/h. CONCLUSIONS: The pharmacokinetics of ropivacaine were independent of dose, but total clearance decreased with time over 24 h. The consistent increase in total plasma concentration during the postoperative epidural infusion contrasted to much less variation in the unbound plasma concentrations of ropivacaine.

Iridoid glycosides of Paederia scandens (IGPS) is a major active component isolated from traditional Chinese herb P. scandens (LOUR.) MERRILL (Rubiaceae). The aim of the present study was to investigate the analgesiceffect of IGPS on spared nerve injury (SNI) model of neuropathic pain. The SNI model in rats was established by complete transection of the common peroneal and tibial distal branches of the sciatic nerve, leaving the sural branch intact. The mechanical withdrawal threshold (MWT) in response to mechanical stimulation was measured by electronic von Frey filaments on day 1 before operation and on days 1, 3, 5, 7, 10, and 14 after operation, respectively. Nitric oxide synthase (NOS) activity and nitric oxide (NO) production of spinal cord were measured by spectrophotometry and its cyclic guanosine monophosphate (cGMP) content by radioimmunoassay, mRNA expression of inducible NOS (iNOS) and protein kinase G type I (PKG-I, including PKG ?? and PKG I?) of spinal cord were analyzed by RT-PCR. There was a marked mechanical hypersensitivity response observed on day 1 after operation in SNI model, which accompanied with decreased MWT. Treatment with IGPS (70, 140, 280 mg/kg) significantly alleviated SNI-induced mechanical hypersensitivity response evidenced by increased MWT; as well as markedly decreased NOS activity, NO and cGMP levels. At the same time, IGPS (70, 140, 280 mg/kg) could also inhibit mRNA expression of iNOS, PKG ?? and PKG I? in the spinal cord. The results suggested that IGPS possesses antinociceptive effect, which may be partly related to the inhibition of NO/cGMP/PKG signaling pathway in the rat SNI model of neuropathic pain. PMID:22698486

Full Text Available Mousa Daradka, Zuhair Bani IsmailDepartment of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, Jordan University of Science and Technology, Irbid, JordanAbstract: Twenty adult female goats affected with chronic mastitis were subjected to mastectomy or hemimastectomy under subarachnoid regional analgesia using a ketamine-lidocaine combination. Ketamine at 1.5 mg/kg and lidocaine hydrochloride at 1.25 mg/kg were administered intrathecally at the lumbosacral intervertebral space. Goats were then subjected to a 120-minute observation period for systemic or neurotoxic symptoms such as agitation, restlessness, hind limb paralysis, or seizures. In addition, analgesia of the caudal abdominal region and signs of systemic sedation were scored on a scale of 0–3. Heart rate, respiratory rate, and rectal temperature were also recorded prior to (baseline values and at 5, 15, 30, 60, 90, and 120 minutes after administration. Mastectomy or hemimastectomy operation was carried out after full assurance of the analgesiceffect on the udder and caudal abdominal region. Time of onset of surgical analgesia (score 3 was achieved at 15 minutes and lasted for 60 minutes. Maximal sedation score was recorded at 15 minutes and lasted for 60 minutes, then decreased thereafter, with the lowest sedation score recorded at 120 minutes. There was a significant (P<0.05 rise in heart rate at some point between 5–90 minutes, while the respiratory rate and rectal temperature did not change significantly from baseline values. Postoperatively, animals did not show any signs of pain or discomfort. Follow-up on the operated goats showed that all wounds were fully healed without any significant complications. In goats, intrathecal administration of ketamine-lidocaine combination resulted in a safe and effective analgesia of the caudal abdominal and udder region sufficient to perform mastectomy or hemimastectomy.Keywords: analgesia, sedation, ruminants, mastectomy

Full Text Available Introduction: Dysmenorrhea is one of the most common gynecologic complications in young women. Given the widespread use of ibuprofen in the treatment of dysmenorrhea, the purpose of present study was to determine the analgesiceffect of ibuprofen by alprazolam in treatment of dysmenorrhea.Materials and Methods: The study was designed as a double blind clinical trial and cross-over study. 40 young female students with dysmenorrhea were randomly divided into two groups of 20. In the first month, the first 20 persons were received ibuprofen (400mg every 8 hours and received placebo nightly from the time of menarche and the second group were received ibuprofen (400mg every 8 hours and a single dose of alprazolam (0.5mg every night for a period of 3 days. Then for the second month, the medicine regime was swiped between two groups. Data were collected using Cox menstrual symptom scale questionnaires. Results: The mean scores of abdominal pain for the day 2 and 4 after treatment in ibuprofen-alprazolam group were lower than those one were observed for ibuprofen- placebo group ( both, P=0.000. Also, the mean scores of low back pain in both day 2 and 4 after treatment with ibuprofen-alprazolam group were significantly lower than those one were observed in the group, which was given ibuprofen- placebo (P=0.000, P=0.005, respectively.Conclusion: According to these findings, it might be proposed ibuprofen-alprazolam compound for relief of dysmenorrheal symptoms, which results in minimum adverse effects of pain on daily living activities as well as pain relief.

Full Text Available The purpose of this study is to prove the analgesiceffects of apitoxin and its mechanism via jaw-opening reflex(JOR and measuring expression of mRNA in Phospholipase and Tryptophan hydroxylase(TPH using RT-PCR. The experiments were carried out on Sprague-Dawley rats(300-400g and mastocytoma (P-185 HTR for JOR and RT-PCR, respectively. Rats anesthetized with thiopental sodium (80mg/kg were used in the Tooth Pulp stimulation induced JOR. The amplitude of a digastric electromyogram (dEMG was recorded during the stimulation at an intensity of 1.5 times the threshold for JOR. Apitoxin used in this experiment was diluted with normal saline by 1:1000. Apitoxin was injected intravenously into the test group while normal saline to the control group. However, it was injected directly into the cell of mastocytoma. We referred to base sequence registered in Genbank in designing primers for RT-PCR. The results were as follows; (1Compared with control group, analgesiceffect started to show right after Sprague-Dawely rats were treated with apitoxin(71.50±8.08 and lasted for 50 minutes. (2As a result of the experiment of RT-PCR, we witnessed significant changes in the degree of expression of phospholipase or rate-limiting enzyme in biosynthesis of prostaglandins with 10?g/? apitoxin.(31.74±18.98%, P<0.05 (3As a result of the experiment of RT-PCR, we witnessed significant changes in the degree of expression of TPH or rate-limiting enzyme in biosynthesis of serotonin with 10?g/? apitoxin.(131.37±16.87%, P<0.05. These results suggest that 10?g/? apitoxin have the most analgesiceffects. This study showed that apitoxin has analgesiceffects and held good for 50 minutes. The injection of apitoxin has brought out changes in the degree of expression of phospholipase and TPH. These results strongly suggest that analgesic mechanism by apitoxin is closely related to prostaglandins and serotonin.

Full Text Available It is well known that the immune reactivity is modulated by gender. In fact, women show a more effective immune response as well as a more frequent development of autoimmune diseases. In particular, 17b-estradiol (E2 in patients with systemic inflammatory diseases leads to an higher production of IgG and IgM in peripheral blood mononucleated cells (PBMC and the secretion of metalloproteinases and IL-6 by synovial fibroblasts. The effect of E2 seems to be partially related to its concentration. In fact, at the physiological concentration, E2 seems to exert a pro-inflammatory effect, while at pharmacological concentrations shows anti-inflammatory effects. Steroid hormones can be converted in downstream hormones along defined pathways. The conversion of dehydroepiandrosterone (DHEA in peripheral macrophages leads to the androgen production. Subsequently the enzyme aromatase converts androgens in estrogens, and its activity is increased by some inflammatory cytokines such as IL-1b, IL-6 and TNF-a. In the synovial fluids of rheumatoid arthritis (RA patients the levels of estrogens result significantly increased compared with controls, showing the consequence of this unbalanced steroid metabolism. Furthermore, the metabolism of estrogens leads to some downstream hydroxylated metabolites, that are not waste products, but still active molecules in the inflammatory response. In fact, it has been found that synovial fluids of RA patients present a different ratio of 16-hydroxylated estrogen metabolites/ 2-hydroxylated metabolites, confirming that also the unbalanced metabolism of estrogens and not only the estrogen concentration seems to be related to the development and worsening of rheumatoid arthritis.

Full Text Available Background and purpose: This study was designed in order to compare the effects of spinal and epidural analgesia on labour and also several maternal and fetal factors in vaginal delivery.Materials and Methods: The study was a randomized clinical trail and participatnts were 120 gravid 1 and gravid 2 women in the active phase of delivery, admitted to the labour room of Fatemieh Hospital in Hamedan in 1381-1382.Sixty patients were randomly divided into two groups of 30, analgesia was induced by single spinal sufentanil injection in one group and, bupivacaine plus lidocaine injection in the other group.Maternal vital signs and pain score were recorded (VAS at 1, 5, 15 and 30 minutes after administration of analgesia and every 30 minutes thereafter. Fetal heart rate every 15 minutes, vaginal examination every hour, urinary output every 4 hours after delivery and the incidence of headache and back pain, one week after delivery were the variables under study.Results: Both groups were matched regarding demographic, gravida and Parity factors. There was no significant difference between groups regarding pain score, (based on VAS,duration of the first and second delivery phase, the incidence of fetal distress, meconium excretion, apgar scores at 1 and 5 minutes after delivery, abnormal laboar, operative or assisted delivery. Average analgesic duration was longer in spinal analgesia than single epidural injection analgesia.Conclusion: Considering the difficulty of the technique, the need for anaestheticianHs supervision and injection repeatition in epidural analgesia, it seems that spinal analgesia is a suitable replacement which is more practical, less expensive, easy to perform and induces a desirable analgesia.

Full Text Available Background: Different Tanacetum species have been widely used in traditional medicine as a remedy for the pain and inflammation since ancient times. Because of the few studies conducted on the mechanism of Tanacetum parthenium (TP, this study has been conducted to determine the effects of TP on pain relief and its action mechanism. Materials and Methods: In this experimental study, 100 male mice (25-35 g were randomly grouped into receivers of distilled water, morphine (0.5 mg/kg, ibuprofen (100 mg/kg, different doses of the extract including 10, 20, 30 and 40 mg/kg of the extract. In order to study the pain relief effect of this herb, two groups were also received naloxon (0.5 mg/kg and naloxon together with the 40 mg/kg of the extract. Animals were injected with 0.9% acetic acid for visceral pain induction. 15 minutes after each injection antinociceptive effects were recorded by counting the number of writhes for 30 minutes. Achieved data were analyzed by SPSS statistical software, Kruskal-Wallis and Dunn post hoc test.Results: 40 mg/kg of the extract of TP caused a significant reduction in the pain response. Group receiving a dose of 40 mg/kg extract had higher antinociceptive effects than the group receiving ibuprofen (p<0.001 but it didn't have any significant difference with the group receiving morphine. Group receiving naloxone had a statistical significant difference with the group receiving 40 mg/kg extract with naloxone and the group receiving 40 mg/kg extract (p<0.001.Conclusion: Antinociceptive activity of TP extract is due to the activation of opioid system, however further studies are needed to be conducted for finding out the suitable position or the role of the antispasmodic effect of TP.

The protein fraction isolated from blood of seal, Phoca groenlandica, has been found to produce hyperalgesic effect on rats exposed to thermic or electrocutaneous nociceptive stimulation, but fail to affect writhes provoked by intraperitoneal injection of acetic acid solution on mice. When combined with morphine, the fraction lowered completely its narcotic analgetic action in the above mentioned tests. On the contrary, these same proteins combined with promedol or fentanil enhanced and prolonged analgetic effect of the latter. Tested in vitro the protein showed neither opioid nor anti-opioid activity. Therefore it is reasonable to suppose that neurophysiological activity of the isolated fraction is due to the peptides formed on enzymatic hydrolysis of proteins in vivo rather than these proteins as such. PMID:1687360

Cecal ligation and puncture (CLP) is the sepsis model that more closely resembles the human pathology, but it is likely to cause suffering to experimental animals. However, it is not clear whether the use of analgesia may affect some parameters evaluated in experimental sepsis research. Therefore, we investigated the effects of fentanyl and tramadol in experimental sepsis in the rat. The following parameters were evaluated: body temperature, body weight, water and food ingestion, mortality, analgesia, blood leukocytes, mean arterial blood pressure, vascular reactivity to phenylephrine, lung myeloperoxidase activity, and plasma levels of IL1-?, glutamic-oxaloacetic, glutamic-pyruvic, lactate, creatinine and urea. While producing significant analgesia, the opioids modify minimally the parameters, with the exception of sepsis-induced hypotension and mortality. Although fentanyl and tramadol can minimize pain and the general suffering of animals submitted to CLP surgery, their effects on cardiovascular parameters as well as in the mortality indicate that their use in experimental sepsis must be done with caution and with all the proper control groups. PMID:22486445

Full Text Available Humans have a long hystory of stimulating and mind-altering substances use. Depressive drugs, including morphine and other narcotics, barbiturates and ethanol, are strongly addictive for susceptible individuals. The phenomenon is most striking in the case of opiates. Morphine is an alkaloid of opium. Named after the Roman god of dreams, Morpheus, the compound has potent analgesic properties toward all types of pain. By supstitution of two hydroxylic groups of morphine many natural and semysyntetic derivatives with different pharmacological activity and analgesic action are obtained. Determinations and quantifications of narcotic analgesics in drug addicts are important in forensic medicine and clinical toxicology. With development of highly sensitive chromatography technique (HPLC-GC, GH-MS, more and more substances are determined, including opioid drugs: morphine, codeine, dyhydrocodeine, and heroin and 6-monoacetyl morphine. Hair analysys by HPLC/MS spectroscopy is an effective forensic tool for determining the use of abused drugs. The “fingerprint” for heroin in the mixture with the other substances(1-10 components is determined by 1D-TOCSY NMR.

Full Text Available Abstract Substance P (SP is a neuropeptide well known for its contribution to pain transmission in the spinal cord, however, less is known about the possible modulatory effects of SP. A new study by Gu and colleagues, published in Molecular Pain (2005, 1:20, describes its potential role in feed-forward inhibition in lamina V of the dorsal horn of the spinal cord. This inhibition seems to function through a direct excitation of GABAergic interneurons by substance P released from primary afferent fibers and has a distinct temporal phase of action from the well-described glutamate-dependent feed-forward inhibition. It is believed that through this inhibition, substance P can balance nociceptive output from the spinal cord.

Effects of neutron skin thickness in peripheral nuclear collisions are investigated using the statistical abrasion ablation (SAA) model. The reaction cross section, neutron (proton) removal cross section, one-neutron (proton) removal cross section as well as their ratios for nuclei with different neutron skin thickness are studied. It is demonstrated that there are good linear correlations between these observables and the neutron skin thickness for neutron-rich nuclei. The ratio between the (one-)neutron and proton removal cross section is found to be the most sensitive observable of neutron skin thickness. Analysis shows that the relative increase of this ratio could be used to determine the neutron skin size in neutron-rich nuclei. (nuclear physics)

Background: Inadequate pain control has a significant role in maternal and neonatal health in early post-partum period which interferes with breastfeeding and has a negative influence on child normal growth. The aim of this study is evaluation of subcutaneous methadone effectiveness on post-operative pain control. Materials and Methods: Double blind randomized prospective clinical trial involving 60 term pregnancy patients through 2008 to 2009 Undergo cesarean. Inclusion criteria: Prime gravid candidate of elective cesarean and spinal anesthesia class 1 or 2. Known case of drug allergy and methadone interaction, addiction, uncontrolled medical disease excluded. Case group injected 10 mg of subcutaneous methadone in the site of incision before final suture. Morphine was a pain reliever in follow up examination. Data include mean of pain, nausea and vomiting, MAP, etc., collected and analyzed by independent-T test and Man Whitney test. Results: Although mean usage of morphine between groups was not significant statistically but the mean pain severity (P value cesarean section patients. PMID:25337527

Full Text Available Aim: To evaluate the efficacy of calcitonin in controlling metastatic bone pain. Materials and methods: Patients with bone metastases, with a numerical pain score greater than 4 wererandomized to receive calcitonin 200 IU subcutaneously 6 hourly for 48 hours (n= 10 or normal saline placebo (n = 10 . The parameters measured were the 11-point numerical pain score, ECOG functional capacity score, morphine consumption in 24 hours, duration of pain in 24 hours and subjective assessment of efficacy of treatment by a blinded investigator. Results: There was a statistically significant decrease in pain score at 48 hours (2 vs 6 and 7 days (3 vs 6 in the calcitonin arm as compared to the control arm. The reduction in duration of pain (3 vs 13 and improvement in ECOG (1.5 vs 2.5 score were also statistically significant. Adverse effects were nausea in 5 patients and vomiting in 3 patients on the day of calcitonin administration. This was controlled with antiemetics. There was no significant change in serum calcium level in either group.

Full Text Available The study was carried out on 60 healthy rams and male goats presented for castration in the Surgery Clinics, Department of Clinical Medicine and Surgery, University of Veterinary and Animal Sciences, Lahore. The weight of the animals ranged between 25 and 50 kg and ages between 3 and 6 months. The animals were divided into three groups A, B and C, with 20 animals in each group. In group A, castration was performed under detomidine sedation injected at a dose rate of 50 ?g/kg body weight intramuscularly. In group B, xylazine was administered at a dose rate of 200 ?g/kg body weight intramuscularly. In group C, castration was performed without the use of any sedative agent. However, animals of group C were given normal saline (placebo. Before surgical manipulation, physical examination of each animal was conducted to ascertain the normal health status. From the study it was concluded that detomidine and xylazine produced similar sedative effects but the analgesia was considerably better with the former.

Full Text Available Abstract Background Pain and impaired mobility because of osteoarthritis (OA is common in dogs and humans. Efficacy studies of analgesic drug treatment of dogs with naturally occurring OA may be challenging, as a caregiver placebo effect is typically evident. However, little is known about effect sizes of common outcome-measures in canine clinical trials evaluating treatment of OA pain. Forty-nine client-owned dogs with hip OA were enrolled in a randomized, double-blinded placebo-controlled prospective trial. After a 1 week baseline period, dogs were randomly assigned to a treatment (ABT-116 – transient receptor potential vanilloid 1 (TRPV1 antagonist, Carprofen – non-steroidal anti-inflammatory drug (NSAID, Tramadol - synthetic opiate, or Placebo for 2 weeks. Outcome-measures included physical examination parameters, owner questionnaire, activity monitoring, gait analysis, and use of rescue medication. Results Acute hyperthermia developed after ABT-116 treatment (P P ? 0.01 and tramadol (P ? 0.001 led to improved mobility assessed by owner questionnaire. Nighttime activity was increased after ABT-116 treatment (P = 0.01. Kinetic gait analysis did not reveal significant treatment effects. Use of rescue treatment decreased with treatment in the ABT-116 and Carprofen groups (P R ? ±0.40, P ? 0.005. Placebo treatment effects were evident with all variables studied. Conclusion Treatment of hip OA in client-owned dogs is associated with a placebo effect for all variables that are commonly used for efficacy studies of analgesic drugs. This likely reflects caregiver bias or the phenomenon of regression to the mean. In the present study, outcome measures with significant effects also varied between groups, highlighting the value of using multiple outcome measures, as well as an a priori analysis of effect size associated with each measure. Effect size data from the present study could be used to inform design of future trials studying analgesic treatment of canine OA. Our results suggest that analgesic treatment with ABT-116 is not as effective as carprofen or tramadol for treatment of hip arthritis pain in client-owned dogs.

Full Text Available Objective To investigate the effects and mechanisms of microwave radiation on peripheral lymphocyte subpopulations in Wistar rats.Methods A total of 100 Wistar rats(180-220g were exposed to microwave with different average power densities of 5,10,30 and 60 mW/cm2,and sham exposure of 0mW/cm2 was performed in a control group at the same time.At day 1,7,14 and 28 after microwave irradiation,the changes in peripheral CD3+,CD4+,CD8+ T cells,ratio of CD4+/CD8+ and CD45RA+ B lymphocyte in rats were analyzed by flow cytometry(FCM.Results The CD3+ T cells decreased significantly in 10-30mW/cm2 groups at day 7 and in 5-30 mW/cm2 groups at day 14 after radiation as compared with control group(P < 0.05,and CD4+ T cells decreased significantly in 10mW/cm2 group at day 14 after radiation as compared with control group(P < 0.01.From day 1 to day 14 after radiation,CD8+ T cells showed a reduction in number in all irradiated groups when compared with the control,but statistical significance was only found in the 30mW/cm2 group(P < 0.05.The CD4+/CD8+ ratio increased in 5mW/cm2 group on day 1,while decreased significantly in 5-30mW/cm2 groups on day 14 after radiation as compared with control group(P < 0.05.After microwave exposure,however,CD45RA+ B cells in 30mW/cm2 group at day 1 and in 30-60mW/cm2 groups at day 14 after radiation increased significantly in a dose-dependent manner.Conclusion A definite dosage of microwave radiation,ranging from 5-60mW/cm2,may induce changes in subpopulations of peripheral lymphocytes and cause acute immune function impairment in rats.

AS1069562 is the (+)-isomer of indeloxazine, which had been clinically used as a cerebral activator for the treatment of cerebrovascular diseases with serotonin and norepinephrine reuptake inhibition (SNRI) and neuroprotection. Here, we compared the analgesiceffects of repeated treatment with AS1069562 and duloxetine, a selective SNRI, on pain-related behavior in a rat model of streptozotocin (STZ)-induced diabetic neuropathy. Further, we also evaluated the effects on the expression of neurotrophic factors and nerve conduction velocity. AS1069562 and duloxetine by single daily administration for 4 weeks significantly improved mechanical allodynia in STZ-induced diabetic rats and did not affect plasma glucose level or body weight. Interestingly, the analgesiceffect of AS1069562 continued after a consecutive 1-week treatment discontinuation, although the plasma concentration of AS1069562 was reduced to undetectable levels. In contrast, the efficacy of duloxetine disappeared after treatment discontinuation. Expression analysis demonstrated that AS1069562 significantly restored decreased insulin-like growth factor 1 and fibroblast growth factor 2 mRNA levels in dorsal root ganglion and spinal cord, respectively, whereas duloxetine did not affect the expression levels of neurotrophic factors. In addition, AS1069562 reversed the slowing of nerve conduction velocity. The results of this study indicate that the analgesiceffect of repeated dosing of AS1069562 but not duloxetine is persistent even after a 1-week drug discontinuation in STZ-induced diabetic rats. Restoration of neurotrophic factors may be involved in the curative-like pharmacological effect of this agent. Thus, AS1069562 may potentially offer a better treatment option for patients with painful diabetic neuropathy than duloxetine via different mechanisms. PMID:24211301

Different extracts and fractions from Sideritis candicans Ait. var. eriocephala Webb aerial part were investigated for their analgesic, anti-inflammatory and antimicrobial activities in mice. Results indicated that the extracts assayed showed anti-nociceptive activities because they were able to reduce the nociceptive response to chemical pain stimuli, such as in the acetic acid-induced writhing test. Moreover the extracts also possessed anti-inflammatory activity against carrageenan-induced paw oedema and TPA-induced ear oedema, being the chloroform fraction the most active. Further fractionation and analysis of this fraction revealed that the analgesic and anti-inflammatory activities found could be related in part to the presence of phytosterols, alpha and beta amyrin triterpenic derivatives and ent-kaurene type diterpenes in this species, since some of these compounds are endowed with these activities. PMID:15234765

Vernonia amygdalina possesses several bioactive compounds and is used in traditional medicines of southwestern Uganda, along with other regions. Its analgesic potential has not been investigated thus far. The present study examines the antinociceptive potential of the aqueous leaf extract (50-200 mg/kg) using three models of nociception (acetic acid-induced writhing, formalin test, and tail-flick test), antiplasmodial activity, and toxicology of the extract. The results show the extract significantly inhibits acetic acid-induced writhing and the formalin test in mice but did not give a potent effect in the tail-flick test, suggesting that the extract may have peripheral and central analgesic properties. The extract also exhibited significant antiplasmodial activity in mice against Plasmodium berghei with 73% inhibition in the group that received a dose of 200 mg/kg i.p. daily for 4 days. Toxicology results show no clinical signs of toxicity or adverse toxicological effects in the treated groups, except for a significant decrease in red blood cell count and a dose-dependent increase in serum bilirubin. These changes were within control values based on historical reference ranges at doses of 500-2,000 mg/kg/day for 14 consecutive days as compared to the control. This study supports the traditional use of V. amygdalina as an alternative therapy for malaria and the symptomatic relief of pain usually associated with malaria. PMID:18800909

Previous work has demonstrated that nonspeech sounds with the appropriate spectral characteristics can affect the identification of speech sounds [Lotto and Kluender, Percept. Psychophys. 60, 602-619 (1998)]. It has been proposed that these spectral context effects are due to interactions in the peripheral auditory system. For example, they could be the result of masking at the auditory nerve or of auditory enhancement effects that have been demonstrated to be monaural [Summerfield and Assmann, Percept. Psychophys. 45, 529-536 (1989)]. To examine the locus of the context effect, synthesized syllables varying from /da/ to /ga/ were preceded by single-formant stimuli that mimicked the third formant of the syllables /al/ and /ar/. The nonspeech stimulus was presented either to the same or opposite ear as the target speech stimulus. Subjects speech identifications were shifted as a function of context in predicted directions for both presentation conditions. However, the size of the shift was smaller when the context was in the ear contralateral to the target syllable. These results agree well with similar results for speech contexts. The data suggest that the context effects occur at multiple levels of the auditory system and are not simply examples of masking or auditory enhancement.

Full Text Available The effect of oxidative stress–induced by hydrogen peroxide (H2O2 on the analgesiceffect of xylazine and dipyrone in 7-14 days old chicks was studied, compared with the control group that given plane tap water. H2O2, 0.5 % in water, induced oxidative stress in chicks by significantly lowering glutathione, rising malondialdehyde in plasma, whole brain during the day 7th, 10th, 14th of chicks old in comparison with the control group. The analgesic median effective doses (ED50 of xylazine and dipyrone in the control group were determined to be 0.79 and 65.3 mg/kg, intramuscularly (i.m., respectively whereas H2O2 treated groups decreased these values to be 0.31 and 37.2 mg/kg, i.m. by 61 and 43%, respectively. Intramuscular injection of xylazine and dipyrone at 0.5, 70 mg/kg respectively causes analgesia from electro-stimulation induced pain in 50, 66.67% respectively in control groups whereas H2O2 treated chicks increases the analgesic efficacy to be 83.33 and 83.33% respectively. Xylazine and dipyrone injection at 1 and 100 mg/kg, i.m. 15 minutes before formaldehyde injection in right planter foot of stressed chicks causes analgesia from pain induced by formaldehyde through significant increases in onset of lifting of formaldehyde injected foot, significantly decreases its lifting numbers, decreases the time elapsed of lifting of formaldehyde injected foot in comparison with the stressed control group that injected with saline in right planter foot. The data of this study indicate that H2O2-induced oxidative stress potentiate the analgesic efficacy of the central and peripheralanalgesics of xylazine and dipyrone in chicks.

Perioperative injection of analgesic agents is widely used for postoperative pain control following knee arthroscopy. This prospective, randomized, double-blind study explored whether a preoperative analgesic injection offered better pain control than a postoperative injection. Patients undergoing knee arthroscopy under general anesthesia were randomized to receive a standardized combination of intra-articular bupivacaine, morphine, and epinephrine administered either 20 minutes prior to incision or at the end of the procedure. Outcome measures included visual analog pain scores at 0, 30, 60, 90, and 120 minutes after the procedure, total recovery room fentanyl consumption, total oral narcotics consumption for the first 24 hours after surgery, and a validated pain and satisfaction instrument. Of the 22 patients enrolled in the study, 21 successfully completed the study protocol. Pain scores, narcotics consumption, and overall patient satisfaction were not significantly different between the two groups. These findings indicate the timing of intra-articular analgesic injections during outpatient knee arthroscopy, either preoperatively or postoperatively, may be at the discretion of the surgeon. PMID:15742593

Divalent cations, such as calcium and magnesium, are constantly present in extracellular compartment of most organisms. Modification of extracellular concentrations of divalent ions causes changes in physiologic functions, such as excitability and conduction of the nerves. The present study was designed to investigate and compare the effects of calcium and magnesium on nerve conduction and lidocaine-induced nerve conduction block. The aim of our study was to contribute to better understanding of physiological and pharmacological roles of divalent cations. Experiments were conducted on the sciatic nerves by using the sucrose-gap recording technique. We evaluated the effects of test solutions containing different calcium or magnesium concentrations, prepared with or without lidocaine, on compound action potentials to determine physiological and pharmacological roles of these cations. After the control recordings, the nerve was exposed to Ringer's solution containing 0, 1.9, 3.8 mM Ca2+ and 1.9 and 3.8 mM Mg2+ with or without 1 mM lidocaine. Decreasing the Ca2+ concentrations in Ringer's solution with or without lidocaine enhanced both tonic and phasic blocks. However, increased Mg2+ concentration did not change the tonic blocks but increased the phasic blocks. In conclusion, the results suggested but not prove that Ca2+ and Mg2+ may have different mechanisms of action on peripheral nerves. While Ca2+ directly affects the gating of Na+ channels, action of Mg2+ can be explained by surface charge theory. PMID:12856822

The endocannabinoid system consists of endogenous arachidonic acid derivates that activate cannabinoid receptors. The two most prominent endocannabinoids are anandamide and 2-arachidonoyl glycerol. In obesity, increased concentrations of circulating and tissue endocannabinoid levels have been described, suggesting increased activity of the endocannabinoid system. Increased availability of endocannabinoids in obesity may over-stimulate cannabinoid receptors. Blockade of cannabinoid type 1 (CB1) receptors was the only successful clinical development of an anti-obesity drug during the last decade. Whereas blockade of CB1 receptors acutely reduces food intake, the long-term effects on metabolic regulation are more likely mediated by peripheral actions in liver, skeletal muscle, adipose tissue, and the pancreas. Lipogenic effects of CB1 receptor signalling in liver and adipose tissue may contribute to regional adipose tissue expansion and insulin resistance in the fatty liver. The association of circulating 2-arachidonoyl glycerol levels with decreased insulin sensitivity strongly suggests further exploration of the role of endocannabinoid signalling for insulin sensitivity in skeletal muscle, liver, and adipose tissue. A few studies have suggested a specific role for the regulation of adiponectin secretion from adipocytes by endocannabinoids, but that has to be confirmed by more experiments. Also, the potential role of CB1 receptor blockade for the stimulation of energy expenditure needs to be studied in the future. Despite the current discussion of safety issues of cannabinoid receptor blockade, these findings open a new and exciting perspective on endocannabinoids as regulators of body weight and metabolism. PMID:20054157

Taheebo, the purple inner bark of the Bignoniaceae tree Tabebuia avellanedae Lorentz ex Griseb, which is found in tropical rain forests in northeastern Brazil, has been used as a traditional medicine for various diseases for more than 1,500 years. In the current study, various animal models were used to demonstrate the analgesic and anti-inflammatory properties of its ethanolic extract, thereby investigating its potential as a therapeutic treatment for diseases with pain and inflammation. In the hot plate and writhing tests for the in vivo analgesiceffect test of Taheebo, a 200 mg/kg dose of the extract induced a significant anti-nociceptive effect and increased the pain threshold by approximately 30% compared with the control. In vascular permeability and tetradecanoylphorbol acetate (TPA)?, arachidonic acid- and carrageenan-induced paw edema tests for anti-inflammatory effects, treatment with 200 mg/kg Taheebo led to significant anti-inflammatory effects and inhibited inflammation by 30-50% compared with the control. At 100 mg/kg, the extract decreased the levels of pain and inflammation in all tested models, but the degree of inhibition was not statistically significant. The results suggest that the ethanolic extract of the inner bark of Tabebuia avellanedae has the potential to be developed as a therapeutic or supportive drug against diseases with accompanying pain and inflammation, including osteoarthritis. PMID:22825254

Full Text Available Cristina Meregalli,1 Cecilia Ceresa,1 Annalisa Canta,1 Valentina Alda Carozzi,1 Alessia Chiorazzi,1 Barbara Sala,1 Norberto Oggioni,1 Marco Lanza,2 Ornella Letar,i2 Flora Ferrari,2 Federica Avezza,1 Paola Marmiroli,1 GianFranco Caselli,2 Guido Cavaletti11Department of Neuroscience and Biomedical Technologies, University of Milan-Bicocca, 2Pharmacology and Toxicology Department, Rottapharm | Madaus Research Center, Monza, ItalyAbstract: Although bortezomib (BTZ is the frontline treatment for multiple myeloma, its clinical use is limited by the occurrence of painful peripheral neuropathy, whose treatment is still an unmet clinical need. Previous studies have shown chronic BTZ administration (0.20 mg/kg intravenously three times a week for 8 weeks to female Wistar rats induced a peripheral neuropathy similar to that observed in humans. In this animal model of BTZ-induced neurotoxicity, the present authors evaluated the efficacy of CR4056, a novel I2 ligand endowed with a remarkable efficacy in several animal pain models. CR4056 was administered in a wide range of doses (0.6–60 mg/kg by gavage every day for 2–3 weeks in comparison with buprenorphine (Bupre (28.8 µg/kg subcutaneously every day for 2 weeks and gabapentin (Gaba (100 mg/kg by gavage every day for 3 weeks. Chronic administration of BTZ reduced nerve conduction velocity and induced allodynia. CR4056, Bupre, or Gaba did not affect the impaired nerve conduction velocity. Conversely, CR4056 dose-dependently reversed BTZ-induced allodynia (minimum effective dose 0.6 mg/kg. The optimal dose found, 6 mg/kg, provided a constant pain relief throughout the treatment period and without rebound after suspension, being effective when coadministered with BTZ, starting before or after allodynia was established, or when administered alone after BTZ cessation. A certain degree of tolerance was seen after 7 days of administration, but only at the highest doses (20 and 60 mg/kg. Bupre was effective only acutely, since tolerance was evident from the fourth day onwards. Gaba showed a significant activity only at the fourth day of treatment. CR4056, over the range of concentrations of 3–30 µM, was unable to hinder BTZ cytotoxicity on several tumor cell lines, which could indicate that this substance does not directly interfere with BTZ antitumor activity. Therefore, CR4056 could represent a new treatment option for BTZ-induced neuropathic pain.Keywords: imidazoline I2 receptor ligand, antinociception, allodynia, neuropathic pain, bortezomib

The history of development of new concepts in pharmacology is a highly interesting topic. This review discusses scientific insights related to palmitoylethanolamide (PEA) and its progression over a period of six decades, especially in light of the work of the science sociologists, Ludwig Fleck and Thomas Kuhn. The discovery of the cannabis receptors and the nuclear peroxisome proliferator-activated receptors was the beginning of a completely new understanding of many important homeostatic physiologic mechanisms in the human body. These discoveries were necessary for us to understand the analgesic and anti-inflammatory activity of PEA, a body-own fatty amide. PEA is a nutrient known already for more than 50 years. PEA is synthesized and metabolized in animal cells via a number of enzymes and has a multitude of physiologic functions related to metabolic homeostasis. PEA was identified in the 1950s as a therapeutic principle with potent anti-inflammatory properties. Since 1975, its analgesic properties have been noted and explored in a variety of chronic pain states. Since 2008, PEA has been available as a nutraceutical under the brand names Normast® and PeaPure®. A literature search on PEA meanwhile has yielded over 350 papers, all referenced in PubMed, describing the physiologic properties of this endogenous modulator and its pharmacologic and therapeutic profile. This review describes the emergence of concepts related to the pharmacologic profile of PEA, with an emphasis on the search into its mechanism of action and the impact of failing to identify such mechanism in the period 1957–1993, on the acceptance of PEA as an anti-inflammatory and analgesic compound. PMID:23964161

Full Text Available Jan M Keppel Hesselink Department of Pharmacology, University of Witten/Herdecke, Witten, Germany Abstract: The history of development of new concepts in pharmacology is a highly interesting topic. This review discusses scientific insights related to palmitoylethanolamide (PEA and its progression over a period of six decades, especially in light of the work of the science sociologists, Ludwig Fleck and Thomas Kuhn. The discovery of the cannabis receptors and the nuclear peroxisome proliferator-activated receptors was the beginning of a completely new understanding of many important homeostatic physiologic mechanisms in the human body. These discoveries were necessary for us to understand the analgesic and anti-inflammatory activity of PEA, a body-own fatty amide. PEA is a nutrient known already for more than 50 years. PEA is synthesized and metabolized in animal cells via a number of enzymes and has a multitude of physiologic functions related to metabolic homeostasis. PEA was identified in the 1950s as a therapeutic principle with potent anti-inflammatory properties. Since 1975, its analgesic properties have been noted and explored in a variety of chronic pain states. Since 2008, PEA has been available as a nutraceutical under the brand names Normast® and PeaPure®. A literature search on PEA meanwhile has yielded over 350 papers, all referenced in PubMed, describing the physiologic properties of this endogenous modulator and its pharmacologic and therapeutic profile. This review describes the emergence of concepts related to the pharmacologic profile of PEA, with an emphasis on the search into its mechanism of action and the impact of failing to identify such mechanism in the period 1957–1993, on the acceptance of PEA as an anti-inflammatory and analgesic compound. Keywords: palmitoylethanolamide, sociology, science, paradigm, peroxisome proliferator-activated receptor-alpha, nutraceutical

The history of development of new concepts in pharmacology is a highly interesting topic. This review discusses scientific insights related to palmitoylethanolamide (PEA) and its progression over a period of six decades, especially in light of the work of the science sociologists, Ludwig Fleck and Thomas Kuhn. The discovery of the cannabis receptors and the nuclear peroxisome proliferator-activated receptors was the beginning of a completely new understanding of many important homeostatic physiologic mechanisms in the human body. These discoveries were necessary for us to understand the analgesic and anti-inflammatory activity of PEA, a body-own fatty amide. PEA is a nutrient known already for more than 50 years. PEA is synthesized and metabolized in animal cells via a number of enzymes and has a multitude of physiologic functions related to metabolic homeostasis. PEA was identified in the 1950s as a therapeutic principle with potent anti-inflammatory properties. Since 1975, its analgesic properties have been noted and explored in a variety of chronic pain states. Since 2008, PEA has been available as a nutraceutical under the brand names Normast® and PeaPure®. A literature search on PEA meanwhile has yielded over 350 papers, all referenced in PubMed, describing the physiologic properties of this endogenous modulator and its pharmacologic and therapeutic profile. This review describes the emergence of concepts related to the pharmacologic profile of PEA, with an emphasis on the search into its mechanism of action and the impact of failing to identify such mechanism in the period 1957-1993, on the acceptance of PEA as an anti-inflammatory and analgesic compound. PMID:23964161

Full Text Available The present study was carried out to investigate the anti-inflammatory, antipyretic and analgesiceffect of the crude ethanol extract of Azadirachta indica leaves on experimental rat model at three different dose levels- 100, 200 and 300 mg/kg, respectively. Hot plate test were used to assess analgesic activity, formalin induced inflammation was used for anti-inflammatory study and baker’s yeast was used to induce pyrexia. Acute toxicity test was also performed in rats after administration of the extract orally at high dose level (4 g/kg. In addition, ethanol extract obtained from Azadirachta indica leaves at different doses and different periods of study showed significant effect (p<0.05 compared to control. For analgesic study, the extract at 100 mg/kg showed a slow but time dependent effect, at 200 mg/kg, its effect was noticed in all the periods although still time dependent and at 300 mg/kg, the effect was significant in all the periods and long-lasting at the final minutes (90 min with values expressed in mean±SEM of 14.0±1.41 which was significant (*p<0.05 compared to control and all other groups. The anti-inflammatory study of the ethanolic extract of Azadirachta indica showed a time and dose dependent effect at different periods. It’s effect was noticed in all doses but was most significant (**p<0.05 in group 4 which was given 300 mg/kg of the extract with a value of 40.6±8.80 expressed in mean±SEM compared to control and all other groups. The extract at all dose showed significant effect (*p<0.05 over control. Its effect was time and dose-dependent. However, the extract attenuated the pain, fever and inflammation induced in the rats at 100, 200 and 300 mg/kg, respectively dose levels but its significant protective effect was noticed at higher doses than low doses and at a longer period of time. In acute toxicity study, no mortality was observed at 4 g/kg dose level.

In a double-blind, randomized study, epidural infusions of low-dose morphine (0.2 mg/h) combined with low-dose bupivacaine (10 mg/h) were compared with epidural infusions of low-dose morphine (0.2 mg/h) alone for postoperative analgesia at rest and during mobilization and cough in 24 patients after elective major abdominal surgery. All patients in addition received systemic piroxicam (20 mg daily). No significant differences were observed between the groups at any assessment of pain at rest (P greater than 0.05), whereas pain in the morphine/bupivacaine group was significantly reduced during mobilization from the supine into the sitting position 12 and 30 h after surgical incision and during cough 8, 12, and 30 h after surgical incision (P less than 0.05). We conclude, that low-dose epidural bupivacaine potentiates postoperative low-dose epidural morphine analgesia during mobilization and cough. Evaluation of postoperative analgesic regimens should include assessment of pain during various activities as different analgesics may have differential effects on pain at rest and during mobilization.

Full Text Available The natural products served as important sources of medicines now a day increasing, as they possess the therapeutic activity. Therefore, the present study was carried out to evaluate the analgesic activity of the petroleum ether and methanol extract of Abelmoschus manihot (Malvaceae leaves using hot plate and tail immersion model. The air-dried, powdered leaves (1000 g were extracted over Soxhlet with petroleum ether and methanol. The crude dried petroleum ether (10 g and methanol (25 g extracts was prepared at the doses of 100, 200 and 400 mg kg-1 and evaluated for analgesic activity using the hot plate and tail immersion test. The results obtained indicate that the extracts possessed significant (p-1 dose as compared with the standard drug. This study showed that the petroleum ether and methanol extracts of Abelmoschus manihot leaves possess potential pharmacological active constituents responsible for inhibition of the analgesiceffect.

Fibromyalgia syndrome (FS) frequently co-occurs with regional pain disorders. This study evaluated how these disorders contribute to FS, by assessing effects of local active vs placebo treatment of muscle/joint pain sources on FS symptoms. Female patients with (1) FS+myofascial pain syndromes from trigger points (n=68), or (2) FS+joint pain (n=56) underwent evaluation of myofascial/joint symptoms [number/intensity of pain episodes, pressure pain thresholds at trigger/joint site, paracetamol consumption] and FS symptoms [pain intensity, pressure pain thresholds at tender points, pressure and electrical pain thresholds in skin, subcutis and muscle in a non-painful site]. Patients of both protocols were randomly assigned to two groups [34 each for (1); 28 each for (2)] to receive active or placebo local TrP or joint treatment [injection/hydroelectrophoresis] on days 1 and 4. Evaluations were repeated on days 4 and 8. After therapy, in active--but not placebo-treated-- groups: number and intensity of myofascial/joint episodes and paracetamol consumption decreased and pressure thresholds at trigger/joint increased (pactive local therapy (days 8 and 11) vs only three patients under active treatment. At a 3-week follow-up, FS pain was still lower than basis in patients not undergoing further therapy and had decreased in those undergoing active therapy from day 8 (p<0.0001). Localized muscle/joint pains impact significantly on FS, probably through increased central sensitization by the peripheral input; their systematic identification and treatment are recommended in fibromyalgia. PMID:20889359

A new once-a-day fentanyl citrate transdermal patch was developed in Japan. We retrospectively investigated analgesic and adverse effects of this drug in 24 patients with lung cancer. All patients were started on this patch by switching from an oral opioid. The mean pain score before switching was 2.45 (0-5); 48 hours after switching, 15 of the 24 patients showed a decreased pain score and the mean score (2.00) was significantly lower than that before switching. Of the 16 patients who had adverse effects of oral opioids, 7 patients showed improvement in their symptoms after switching. Two patients showed adverse effects of the drug but their symptoms were mild, and no patient required dose decrease. This new transdermal patch could be a useful treatment option for cancer pain. PMID:23264661

Full Text Available Objectives : To study the analgesic and anti-nociceptive activity of hydroethanolic extract of Drymaria cordata Willd. Materials and Methods : Wistar rats and Swiss albino mice were used for studying analgesic and anti-nociceptive activity of Drymaria cordata hydroethanolic extract (DCHE at doses 50, 100 and 200 mg/kg p.o. Various models viz. acetic acid induced writhing model (female mice, Eddy?s hot plate (mice and tail flick model (rat for analgesic study and formalin-induced paw licking model (mice were used for anti-nociceptive study. Results : In acetic acid induced writhing model, effect of DCHE was better than the standard drug- indomethacin 10 mg/kg (p.o.. In the hot plate model, the maximum effect was observed at 60 min at a dose of 200 mg/kg p.o., which was higher than the standard drug morphine sulfate (1.5 mg/kg i.p., whereas in the tail flick model, effect was comparable with morphine sulfate. In formalin-induced paw licking model, administration of DCHE completely abolished the early phase at 100 and 200 mg/kg p.o. and in the late phase, the effect of DCHE (200 mg/kg p.o. was higher than indomethacin (10 mg/kg p.o.. Conclusion : DCHE was effective in both non-narcotic and narcotic models of nociception, suggesting its possible action via peripheral and central mechanism. It also abolished the early phase in formalin-induced paw licking model, suggesting complete inactivation of C-fiber at higher dose. The activity can be attributed to the phyto-constituents viz tannins, diterpenes, triterpenes and steroids present in the DCHE extract. In conclusion, DCHE can be developed as a potent analgesic and anti-nociceptive agent in future.

Full Text Available Objective: Moringa oleifera (family Moringaceae has been widely used in African folk medicine, and researchers have recently revealed its anti-inflammatory effects in human. This study aimed to evaluate the analgesic properties of methanolic extracts of M. oleifera in complete Freund’s adjuvant (CFA-induced arthritis in rats. Methods: Adult male Wistar rats, weighing 200 to 220 g, were used in this study. Adjuvant arthritis was induced on day 0 by a single subcutaneous injection of CFA. The prepared extracts from both the root and leaf (200, 300 and 400 mg/kg of M. oleifera were administered intraperitonealy to rats in the treatment groups 0, 3 and 6 d after CFA injection and indomethacin (5 mg/kg was used as a positive control drug. Thermal hyperalgesia and mechanical allodynia were evaluated for the analgesiceffect 0, 3 and 6 d after CFA injection. Combined methanolic root and leaf extracts of M. oleifera (200 mg/kg were also tested for the analgesiceffect.Results: The potency of the root or leaf extracts of M. oleifera (300 and 400 mg/kg was similar to that of indomethacin, resulted in significant reductions in both thermal hyperalgesia and mechanical allodynia in rats with CFA-induced arthritis compared with the control group after 3 and 6 d, respectively (P<0.01 or P<0.05. Combined root and leaf extracts (200 mg/kg of M. oleifera resulted in a significant reduction in thermal hyperalgesia compared with the control group after 3 and 6 d, respectively (P<0.01. Prophylactic injections of combined root and leaf extracts of M. oleifera (200 mg/kg resulted in a significant reduction in thermal hyperalgesia compared with the control group, the root extracts group, and the leaf extracts group after 3 and 6 d, respectively (P<0.01. Conclusion: The methanolic extracts of the root or leaf of M. oleifera are effective in the reduction of pain induced by CFA in rats. A comparison of single and combination therapies of root and leaf extracts also showed a synergistic effect on pain reduction.

Full Text Available Abstract Background We have previously reported that inhibition of astrocytic activation contributes to the analgesiceffects of intrathecal ketamine on spinal nerve ligation (SNL-induced neuropathic pain. However, the underlying mechanisms are still unclear. c-Jun N-terminal kinase (JNK, a member of mitogen-activated protein kinase (MAPK family, has been reported to be critical for spinal astrocytic activation and neuropathic pain development after SNL. Ketamine can decrease lipopolysaccharide (LPS-induced phosphorylated JNK (pJNK expression and could thus exert its anti-inflammatory effect. We hypothesized that inhibition of astrocytic JNK activation might be involved in the suppressive effect of ketamine on SNL-induced spinal astrocytic activation. Methods Immunofluorescence histochemical staining was used to detect SNL-induced spinal pJNK expression and localization. The effects of ketamine on SNL-induced mechanical allodynia were confirmed by behavioral testing. Immunofluorescence histochemistry and Western blot were used to quantify the SNL-induced spinal pJNK expression after ketamine administration. Results The present study showed that SNL induced ipsilateral pJNK up-regulation in astrocytes but not microglia or neurons within the spinal dorsal horn. Intrathecal ketamine relieved SNL-induced mechanical allodynia without interfering with motor performance. Additionally, intrathecal administration of ketamine attenuated SNL-induced spinal astrocytic JNK activation in a dose-dependent manner, but not JNK protein expression. Conclusions The present results suggest that inhibition of JNK activation may be involved in the suppressive effects of ketamine on SNL-induced spinal astrocyte activation. Therefore, inhibition of spinal JNK activation may be involved in the analgesiceffects of ketamine on SNL-induced neuropathic pain.

Background: Limited evidence supports the efficacy of peripheral route fentanyl and local anesthetic combination for postoperative analgesia. Our study was therefore designed to demonstrate the analgesic efficacy of two different doses of fentanyl in combination with bupivacaine for surgical site infiltration in patients undergoing modified radical mastoidectomy (MRM). Materials and Methods: 60 patients undergoing MRM under general anesthesia were randomly allocated into two groups, first group receiving 0.5% bupivacaine at a dose of 2 mg/kg body weight with 50 ?g fentanyl and second group receiving bupivacaine 0.5% at a dose of 2 mg/kg body weight with 100 ?g fentanyl as infiltration of operative field in and around the incision site, after the incision and just before completion of surgery. In postoperative period pain, nausea-vomiting and sedation was recorded at 0 hr, 2, 4, 6, 12 and 24 hrs. Results: Both the combinations of bupivacaine and fentanyl (Group I and Group II) were effective for postoperative analgesia. In both the groups the Visual Analogue Scale (VAS) score was less than 3 at each time interval. None of the patients required rescue analgesia. The comparison of VAS scores at different intervals showed that group II had lower VAS scores at all time points. Conclusions: Fentanyl and bupivacaine combinations in doses of 50 and 100 ?g along with 0.5% bupivacaine at a fixed dose of 2 mg/kg body weight are effective in the management of postoperative pain. Patients who received 100 ?g fentanyl (Group II) had lower VAS scores as compared to the patients who received 50 ?g fentanyl (Group I) with similar side effects.

In recent years a growing debate is about whether botulinum neurotoxins are retrogradely transported from the site of injection. Immunodetection of cleaved SNAP-25 (cl-SNAP-25), the protein of the SNARE complex targeted by botulinum neurotoxin serotype A (BoNT/A), could represent an excellent approach to investigate the mechanism of action on the nociceptive pathways at peripheral and/or central level. After peripheral administration of BoNT/A, we analyzed the expression of cl-SNAP-25, from t...

Diverse studies have shown that magnetic fields can affect behavioral and physiological functions. Previously, we have shown that sinusoidal extremely low frequency magnetic fields and specific pulsed magnetic fields (Cnps) can produce alterations in the analgesia-related behavior of the land snail. Here, we have extended these studies to show an induction of analgesia in mice equivalent to a moderate dose of morphine (5 mg/kg), and the effect of both Cnp exposure and morphine injection on some open-field activity. Cnp exposure was found to prolong the response latency to a nociceptive thermal stimulus (hot plate). Cnp+morphine offset the increased movement activity found with morphine alone. These results suggest that pulsed magnetic fields can induce analgesic behavior in mice without the side effects often associated with opiates like morphine. PMID:14698475

Full Text Available Siddha Yoga Sangraha of Yadavji Trikamji Acharya, states about Mamsyadi kwatha, an Ayurvedic formulation which is said to be effective in minor mental disorders. The ingredients of Mamsyadi kwatha are Jatamamsi (Nardistachys jatamansi DC, Ashwagandha (Withania somnifera Linn and Parasika yavani (Hyoscymus niger Linn, in 8:4:1 ratio respectively. The test formulation was subjected to assess its analgesiceffect. The model selected for the assessment of analgesiceffect was tail flick test, in albino mice. The test formulation possesses analgesiceffect, which is mainly due to its component Parasika yavani.

This Brookhaven National Laboratory (BNL) Web site contains a press release about the recent findings from BNL scientists that smoking reduces levels of a critical enzyme (MAO B) not only in the brain, but in the peripheral organs as well (kidneys, heart, lungs, and spleen). The press release includes images of whole body PET scans showing the distribution of the radiolabeled enzyme in the bodies of a smoker and a nonsmoker -- users can click on the image for a high-resolution version.

Neuropathic pain elevates spinal anandamide (AEA) levels in a way further increased when URB597, an inhibitor of AEA hydrolysis by fatty acid amide hydrolase (FAAH), is injected intrathecally. Spinal AEA reduces neuropathic pain by acting at both cannabinoid CB1 receptors and transient receptor potential vanilloid-1 (TRPV1) channels. Yet, intrathecal URB597 is only partially effective at counteracting neuropathic pain. We investigated the effect of high doses of intrathecal URB597 on allodynia and hyperalgesia in rats with chronic constriction injury (CCI) of the sciatic nerve. Among those tested, the 200 µg/rat dose of URB597 was the only one that elevated the levels of the FAAH non-endocannabinoid and anti-inflammatory substrates, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), and of the endocannabinoid FAAH substrate, 2-arachidonoylglycerol, and fully inhibited thermal and tactile nociception, although in a manner blocked almost uniquely by TRPV1 antagonism. Surprisingly, this dose of URB597 decreased spinal AEA levels. RT-qPCR and western blot analyses demonstrated altered spinal expression of lipoxygenases (LOX), and baicalein, an inhibitor of 12/15-LOX, significantly reduced URB597 analgesiceffects, suggesting the occurrence of alternative pathways of AEA metabolism. Using immunofluorescence techniques, FAAH, 15-LOX and TRPV1 were found to co-localize in dorsal spinal horn neurons of CCI rats. Finally, 15-hydroxy-AEA, a 15-LOX derivative of AEA, potently and efficaciously activated the rat recombinant TRPV1 channel. We suggest that intrathecally injected URB597 at full analgesic efficacy unmasks a secondary route of AEA metabolism via 15-LOX with possible formation of 15-hydroxy-AEA, which, together with OEA and PEA, may contribute at producing TRPV1-mediated analgesia in CCI rats. PMID:23573230

The effect was studied of single or repeat injection administration of indomethacin on the peripheral blood count of gamma-irradiated rats with single whole-body doses (5.5 and 6.0 Gy). It was found that the post-irradiation administration of indomethacin stimulated the recovery of the peripheral granulocyte count. The stimulating effects of indomethacin on the granulocyte level in peripheral blood were also apparent in non-irradiated rats. The unfavourable effect of higher doses of indomethacin became apparent in a decreased red blood cell count in peripheral blood, possibly caused by the ulcerogenic influence of this non-steroid antiinflammatory drug on mucous membrane of the gastrointestinal tract with subsequent bleeding. (author). 2 figs., 15 refs

Aims Multimodal analgesia is thought to produce balanced and effective postoperative pain control. A combined therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) and opiates could result in synergistic analgesia by acting through different mechanisms. Currently there are very few parenterally administered NSAIDs suitable for the immediate postoperative period. Therefore, this study was undertaken to assess the analgesic efficacy, relative potency, and safety of parenteral dexketoprofen trometamol following major orthopaedic surgery. Methods One hundred and seventy-two patients elected for prosthetic surgery, were randomized to receive two intramuscular injections (12 hourly) of either dexketoprofen 50 mg, ketoprofen 100 mg or placebo in a double-blind fashion. Postoperatively, the patient's pain was stabilized, then they were connected to a patient- controlled analgesia system (PCA) of morphine for 24 h (1 mg with 5 min lockout). Results The mean cumulative amount of morphine (CAM) used was of 39 mg in the dexketoprofen group and 45 mg in the ketoprofen group vs 64 mg in the placebo group. (Reduction in morphine use was approximately one-third between the active compounds compared with placebo (adjusted mean difference of ?25 mg between dexketoprofen and placebo and ?23 mg between ketoprofen and placebo. These differences were statistically significant: P ? 0.0003; 95% CI ?35, ?14. Pain-intensity scores were consistently lower with the active compounds, the lowest corresponded to the dexketoprofen-treated patients. Regarding sedation, there were statistically significant differences between the two active compounds and placebo only at the 2nd and 13th hours. Wound bleeding was specifically measured with no statistically significant differences found between all the groups. Conclusions Intramuscular administration of dexketoprofen trometamol 50 mg has good analgesic efficacy both in terms of opioid-sparing effect and control of pain after major orthopaedic surgery. PMID:12580983

Experimental study was made by keeping human peripheral blood lymphocytes under simulated microgravity in a Rotary Cell Culture System bioreactor to investigate the changes that occur in the number of chromosomes, the expression rate of chromosome fragile site, and the expressions of DNA replication- and repair-related genes. Experimental results indicate simulated microgravity has no effect on the numerical chromosome instability of human peripheral blood lymphocytes, but it enhances the structural chromosome instability of human peripheral blood lymphocytes through the inhibition of DNA replication and the reduction of DNA repair. So, the mechanism of chromosome fragile site induced by simulated microgravity can be explained using the changes that occur in the chromosome structure of human peripheral blood lymphocytes, the DNA replication and repair under the effect of simulated microgravity. PMID:24963972

Full Text Available Despite intrinsic capacity of peripheral nerves to regenerate, functional outcomes of peripheral nerves injury remain poor. Nerve ischemia, intra-/perineurial fibrosis and neuroma formation contribute a lot to that. Several authors demonstrated beneficial effects of increased vascularization at the site of injury on peripheral nerves regeneration. The use of highly vascularized autologous tissues (greater omentum as a source of peripheral nerves neovascularization shows promising re-sults. We proposed a surgical technique in which injured peripheral nerves anastomosis was wrapped in a pedicled muscular flap and performed morphological assessment of the efficacy of such technique with the aid of immunohistochemistry. 14 rats (which underwent sciatic nerve transection were operated according to proposed technique. Another 14 rats, in which only end-to-end nerve anastomosis (without muscular wrapping was performed served as controls. Morphological changes were evaluated at 3 weeks and 3 months periods. Higher blood vessel and axon counts were observed in experimental groups at both checkpoints. There was also an increase in Schwann cells and macrophages counts, and less collagen content in pe-ripheral nerves of experimental groups. Axons in neuromas of experimental groups showed a higher degree of arrangement. We conclude that proposed surgical technique provides better vascularisation of injured peripheral nerves, which is beneficial for nerve regeneration.

The present study provides in vitro and in vivo evaluation of arecoline on peripheral nerve regeneration. In the in vitro study, we found that arecoline at 50 ?g/ml could significantly promote the survival and outgrowth of cultured Schwann cells as compared to the controls treated with culture medium only. In the in vivo study, we evaluated peripheral nerve regeneration across a 10-mm gap in the sciatic nerve of the rat, using a silicone rubber nerve chamber filled with the arecoline solution. In the control group, the chambers were filled with normal saline only. At the end of the fourth week, morphometric data revealed that the arecoline-treated group at 5 ?g/ml significantly increased the number and the density of myelinated axons as compared to the controls. Immunohistochemical staining in the arecoline-treated animals at 5 ?g/ml also showed their neural cells in the L4 and L5 dorsal root ganglia ipsilateral to the injury were strongly retrograde-labeled with fluorogold and lamina I-II regions in the dorsal horn ipsilateral to the injury were significantly calcitonin gene-related peptide-immunolabeled compared with the controls. In addition, we found that the number of macrophages recruited in the distal sciatic nerve was increased as the concentration of arecoline was increased. Electrophysiological measurements showed the arecoline-treated groups at 5 and 50 ?g/ml had a relatively larger nerve conductive velocity of the evoked muscle action potentials compared to the controls. These results indicate that arecoline could stimulate local inflammatory conditions, improving the recovery of a severe peripheral nerve injury. PMID:23895157

The role of quantitative sensory testing (QST) in prediction of analgesiceffect in humans is scarcely investigated. This updated review assesses the effectiveness in predicting analgesiceffects in healthy volunteers, surgical patients and patients with chronic pain. A systematic review of English written, peer-reviewed articles was conducted using PubMed and Embase (1980-2013). Additional studies were identified by chain searching. Search terms included 'quantitative sensory testing', 'sensory testing' and 'analgesics'. Studies on the relationship between QST and response to analgesic treatment in human adults were included. Appraisal of the methodological quality of the included studies was based on evaluative criteria for prognostic studies. Fourteen studies (including 720 individuals) met the inclusion criteria. Significant correlations were observed between responses to analgesics and several QST parameters including (1) heat pain threshold in experimental human pain, (2) electrical and heat pain thresholds, pressure pain tolerance and suprathreshold heat pain in surgical patients, and (3) electrical and heat pain threshold and conditioned pain modulation in patients with chronic pain. Heterogeneity among studies was observed especially with regard to application of QST and type and use of analgesics. Although promising, the current evidence is not sufficiently robust to recommend the use of any specific QST parameter in predicting analgesic response. Future studies should focus on a range of different experimental pain modalities rather than a single static pain stimulation paradigm.

Objective: To explore the changes of GADD45A gene expression in human peripheral blood induced by 60Co ? ray irradiation and offer the fundamental materials for the research of boimarker in early diagnosis of radiation damage. Methods: Human peripheral blood was irradiated to 0.05-3 Gy 60Co ?-ray and changes of GADD45A genes in peripheral blood were detected by Real-time fluorescent quantitative PCR. Results: After irradiation, the expression of GADD45A genes in human peripheral blood changes significantly. Specifically, from 0.05 Gy to 0.6 Gy, the expression of GADD45A genes decreased with the increase of irradiation dose. And from 1 Gy to 3 Gy, the expression of GADD45A genes increased with the increase of irradiation dose compared with the control. Conclusion: 60Co ? ray irradiation can induce the changes of GADD45A gene expression in human peripheral blood. And the changes of GADD45A gene shows fine dose-effect relationship from 1 Gy to 3 Gy. From 0.05 Gy to 0.2 Gy, peripheral blood lymphocytes showed stimulation effect. (authors)

Full Text Available This was a randomized double-blinded study; in which 60 ASAI-II adult patients scheduled for major abdominal surgeries (colostomy, radical cystectomy, major gynecological surgery, and abdominal vascular surgery were received standard general anesthesia. Twenty minutes before the anticipated end of surgery, patients were randomized into two equal groups: dexmedetomidine group (group D and morphine group (group M. Group D received dexmedetomidine IV infusion 4µg/kg/h for 15 minutes (1µg/Kg followed by 0.4µg/kg/h for 3h. Group M received morphine sulfate IV (0.07mg/kg. All patients were given a morphine patient controlled analgesia (PCA pump in the post anesthesia care unit (PACU, delivering IV morphine 2mg with a lockout time of 5 minutes if pain score assessed through visual analog scale (VAS was more than 5 at any given 5-min assessment. During the PACU recovery period, morphine consumption; pain and sedation scores; hemodynamic variables (heart rate, mean arterial blood pressure, oxygen saturation and respiratory rate; and postoperative nausea, retching and vomiting (PONV were recorded every 30 min for 3h (study period by a member of staff blinded to the treatment. The study demonstrated that the use of dexmedetomidine led to significant decrease in the total amount of morphine consumed throughout the entire PACU recovery period (P0.05; significant decrease in mean arterial pressure (P0.05; without any significant changes in oxygen saturation (P<0.05 or respiratory rate (P<0.05. In conclusion, dexmedetomidine exhibited both analgesic and sedative properties. The associated cardiovascular protective pharmacological profile and the lack of respiratory depression made it potentially extremely interesting for postoperative analgesia after major abdominal surgeries.

The aim of this study was to evaluate the analgesic and anti-diarrheal activity of the whole plant Boerhavia repens. Sun dried roots, stems, barks and the leaves of B. repens were extracted using methanol at room temperature. The crude methanol extract was fractionated in two different solvents using Petroleum ether and Carbon Tetrachloride. The peripheralanalgesic activity was evaluated by acetic acid induced Writhing method. The petroleum ether soluble materials at a dose of 400 mg/kg exhi...

Full Text Available The ethanolic extract of the leaves of Mimosa pudica at the doses of 200 and 400mg/kg was tested for anti-inflammatory and analgesic activity. The extract produced dose dependent and significant inhibition of carrageenan induced paw oedema.The analgesic activity was found to be more significant on the acetic acid induced writhing model (p<0.001 than the tail flick model (p<0.001. So the extract inhibits predominantly the peripheral mechanism. The presence of flavonoids in the ethanolic extract may be contributory to its analgesic and anti-inflammatory activity.

Different desensitizing agents have been used in the treatment of dentinal hypersensitivity, however, some presented treatments are still frustrating. The purpose of this study was to evaluate the analgesiceffect of the low-intensity GaAlAs laser (?= 830 nm) in the treatment of dentinal hypersensitivity after mechanical and thermal stimuli, and compared it with the 33% sodium fluoride paste. Thirty two teeth with dentinal hypersensitivity were selected and randomly divided into two groups. For the laser group, each tooth was irradiated by a dose of 6 J/cm2 during two minutes and half on the buccal side. The paste group was treated with a NaF/kaolin/glycerin (33:33:33) paste by burnishing the sensitive surface during four minutes. The sensitivity degree was measured before the beginning of the experiment, 24 h, 48 h, 72 h, 120 h, 15 days and 30 days after the first application. The results indicate that the dentinal hypersensitivity significantly diminished for the paste group after dental explorer. Regarding to air-blast, no significant differences were observed between the groups. Both of them were effective in reducing pain of the dentine hypersensitive after 120 h. (author)

Cannabinoids and opioids both produce analgesia through a G-protein-coupled mechanism that blocks the release of pain-propagating neurotransmitters in the brain and spinal cord. However, high doses of these drugs, which may be required to treat chronic, severe pain, are accompanied by undesirable side effects. Thus, a search for a better analgesic strategy led to the discovery that delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent of marijuana, enhances the potency of opioids such as morphine in animal models. In addition, studies have determined that the analgesiceffect of THC is, at least in part, mediated through delta and kappa opioid receptors, indicating an intimate connection between cannabinoid and opioid signaling pathways in the modulation of pain perception. A host of behavioral and molecular experiments have been performed to elucidate the role of opioid receptors in cannabinoid-induced analgesia, and some of these findings are presented below. The aim of such studies is to develop a novel analgesic regimen using low dose combinations of cannabinoids and opioids to effectively treat acute and chronic pain, especially pain that may be resistant to opioids alone. PMID:14706563

The uses of non-steroidal anti-inflammatory drugs (NSAIDs) are limited by a variety of side effects. So research on preparing new analgesic agents is important. According to some reports about the analgesic activity of hydrazide and hydrazine derivatives a new series of these compounds were synthesized in order to obtain new analgesic compounds. The final compounds 10a-10e and 15a-15d were prepared by condensation of corresponding hydrazides 7,8 and 11-14 with different aldehydes 9a-9e. The structures of all synthesized compounds were confirmed by means of FT-IR, 1H-NMR and Mass spectra. All compounds were evaluated for their analgesic activities by abdominal constriction test (writhing test). Most of the synthesized compounds induced significant reduction in the writhing response when compared to control and compound 15 was more potent than mefenamic acid in the writhing test. PMID:24523751

The radionculide therapy of bone metastases is an unspecific palliative treatment of metastatic skeletal pain especially useful in patients suffering in multiple sites. In these cases the long-term administration of increasing doses of analgesics such as opiate which have important side effects can be reduced. The aim of this therapy is pain relief and improvement of quality of life in patients with advanced cancer. This report is focusing on options, indications and contraindications of the radionuclide therapy of metastases and on used radionuclides such as Strontium-89, Yttrium-90, Rhenium-186 (188) and Samarium-153. In oncology, the analgesic therapy using boneseeking radiopharmaceuticals in combination to drug administration should gain more importance because this therapy can be administered on an outpatient basis. (orig.)

OBJECTIVEChronic diabetic peripheral neuropathic pain (DPNP) is difficult to treat, with treatment regimens often inadequate at controlling pain and limited by side effects and drug tolerance. Secondary parameters, such as quality of sleep and mood, may also be important for successful DPNP management. The objectives of this study were to compare the analgesic efficacy of pregabalin, amitriptyline, and duloxetine, and their effect on polysomnographic sleep, daytime functioning, and quality of...

In two experiments with European eel (Anguilla anguilla L., 1758) the effects of flumequine (FQ), oxytetracycline (OTC) and furazolidone (FZ) on peripheral blood leucocytes were tested using measurements of differential white blood cell counts in blood smears, flow cytometry and respiratory burst activity of adherent cells. Results revealed that FQ and OTC affected (different) leucocyte populations, whereas no effect of FZ was detected in these experiments. These effects should be taken into ...

Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h before heat injury (47 degrees C, 7 min) and naloxone infiltration s.c. (0.2 mg) 2.5 h after the heat injury. Hyperalgesia to mechanical and heat stimuli were examined using von Frey hairs and thermodes, and pain was rated using a visual analogue scale. The burns produced significant hyperalgesia, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain.

Objectives. To compare the analgesic efficacy of intrathecal clonidine and fentanyl added to bupivacaine after cesarean section. Methods. Ninety patients scheduled for cesarean section under spinal anesthesia were randomly allocated to one of the three following groups to receive bupivacaine 10?mg combined with 75?µg clonidine (group C), bupivacaine 10?mg combined with 0.5?mL fentanyl (group F), and bupivacaine 10?mg combined with 0.5?mL distilled water (group P), intrathecally. The time to first analgesic request, analgesic requirement in the first 24 hours after surgery, sensory and motor blockade onset time, duration of sensory and motor blockade, the incidence of hypotension, ephedrine requirements, bradycardia, and hypoxemia were recorded. Results. The duration of anesthesia in clonidine group (275.10 ± 96.09) was longer compared to the placebo (211.73 ± 74.80) and fentanyl (192.33 ± 30.36) groups. This difference between group C versus F (P = 0.006) and P groups (P < 0.001) was significant. Similarly, the mean time to first analgesic request was also longer in group C (519.44 ± 86.25) than in groups F (277.88 ± 94.25) and P (235.43 ± 22.35?min). This difference between group C versus F (P < 0.001) and P groups (P < 0.001) was significant. Conclusion. Intrathecal clonidine 75?µg with bupivacaine prolonged the time to first analgesic request compared to fentanyl; however, the total analgesic consumption within the first 24?h postoperative was similar in fentanyl and clonidine groups following cesarean section. This trial is registered with ACTRN12611000909921 and ClinicalTrials.gov NCT01425658. PMID:24649361

The aim of this study was to investigate the mutagenic and anti-mutagenic effects of Ecballium elaterium (EE) fruit juice which has an anti inflammatory effect using in vitro human peripheral lymphocytes. For the investigating the mutagenic effects of EE fruit juice, human peripheral lymphocytes was treated with three doses (18, 36 and 72 microl/1) of fruit juice alone for 24 and 48 h. For the investigating the anti-mutagenic effects of the EE fruit juice, the human lymphocytes also treated with the mixture of the fruit juice and 0.25 microg/ml MMC. EE fruit juice induced the percentage of total CA when used alone (especially the percentage of structural CA than the percentage of the numerical CA) and synergically induced the percentage of total CA when used as a mixture with MMC. EE fruit juice did not affect the SCE frequency for 24 and 48 h treatment time. In contrast, EE and MMC as a mixture, sinergically induced the SCE frequency at the highest concentration for 48 h treatment time only. EE alone did not decrease the RI while it decreased the MI as a dose dependent manner. EE and MMC as a mixture have the higher cytotoxic effect than the cytotoxic effects of EE alone. As a result, it can be concluded that, EE had no anti-mutagenic effect while EE had a mutagenic and a cytotoxic effect in human peripheral lymphocytes. PMID:16871781

Full Text Available Abstract Background Doxazosin and its role as an antihypertensive agent have come under recent scrutiny as a result of the early termination of that treatment arm in ALLHAT. It is unclear why the cardiovascular (CV event rate in this randomized, controlled trial (RCT, especially heart failure, is higher in those treated with a doxazosin-based regimen than with a chlorthalidone based-regimen. There has been little work in the past to summarize information on peripheral alpha-1 antagonists that may be helpful in evaluating the results of this randomized controlled trial. Methods Using Medline and the Cochrane databases, we performed a comprehensive review of the literature on the use of peripheral alpha-1 antagonists as antihypertensive agents, focusing on available information that could explain the excess cardiovascular events observed in the Antihypertensive and Lipid-Lowering Treatment to prevent Heart Attack Trial (ALLHAT. Results Minimal data were available concerning the effects of peripheral alpha-1 antagonists on CV endpoints. A multitude of short-term studies-ranging from small observational studies to short-term moderate-sized RCTs – focused on safety, efficacy, and tolerability, and some studies investigated the physiologic effects of these agents. These previously reported studies reveal associations with weight gain, fluid retention, and neurohormonal changes among various populations of those treated with peripheral alpha-1 antagonists. Conclusion These findings suggest several possible mechanisms by which doxazosin may be inferior to low-dose diuretics as antihypertensive therapy for the prevention of heart failure.

Full Text Available The pineal hormone, melatonin (N-acetyl-5-methoxytryptamine, shows potent receptor-dependent and -independent actions, which participate in blood pressure regulation. The antihypertensive effect of melatonin was demonstrated in experimental and clinical hypertension. Receptor-dependent effects are mediated predominantly through MT1 and MT2 G-protein coupled receptors. The pleiotropic receptor-independent effects of melatonin with a possible impact on blood pressure involve the reactive oxygen species (ROS scavenging nature, activation and over-expression of several antioxidant enzymes or their protection from oxidative damage and the ability to increase the efficiency of the mitochondrial electron transport chain. Besides the interaction with the vascular system, this indolamine may exert part of its antihypertensive action through its interaction with the central nervous system (CNS. The imbalance between the sympathetic and parasympathetic vegetative system is an important pathophysiological disorder and therapeutic target in hypertension. Melatonin is protective in CNS on several different levels: It reduces free radical burden, improves endothelial dysfunction, reduces inflammation and shifts the balance between the sympathetic and parasympathetic system in favor of the parasympathetic system. The increased level of serum melatonin observed in some types of hypertension may be a counter-regulatory adaptive mechanism against the sympathetic overstimulation. Since melatonin acts favorably on different levels of hypertension, including organ protection and with minimal side effects, it could become regularly involved in the struggle against this widespread cardiovascular pathology.

The pineal hormone, melatonin (N-acetyl-5-methoxytryptamine), shows potent receptor-dependent and -independent actions, which participate in blood pressure regulation. The antihypertensive effect of melatonin was demonstrated in experimental and clinical hypertension. Receptor-dependent effects are mediated predominantly through MT1 and MT2 G-protein coupled receptors. The pleiotropic receptor-independent effects of melatonin with a possible impact on blood pressure involve the reactive oxygen species (ROS) scavenging nature, activation and over-expression of several antioxidant enzymes or their protection from oxidative damage and the ability to increase the efficiency of the mitochondrial electron transport chain. Besides the interaction with the vascular system, this indolamine may exert part of its antihypertensive action through its interaction with the central nervous system (CNS). The imbalance between the sympathetic and parasympathetic vegetative system is an important pathophysiological disorder and therapeutic target in hypertension. Melatonin is protective in CNS on several different levels: It reduces free radical burden, improves endothelial dysfunction, reduces inflammation and shifts the balance between the sympathetic and parasympathetic system in favor of the parasympathetic system. The increased level of serum melatonin observed in some types of hypertension may be a counter-regulatory adaptive mechanism against the sympathetic overstimulation. Since melatonin acts favorably on different levels of hypertension, including organ protection and with minimal side effects, it could become regularly involved in the struggle against this widespread cardiovascular pathology. PMID:25299692

The pineal hormone, melatonin (N-acetyl-5-methoxytryptamine), shows potent receptor-dependent and -independent actions, which participate in blood pressure regulation. The antihypertensive effect of melatonin was demonstrated in experimental and clinical hypertension. Receptor-dependent effects are mediated predominantly through MT1 and MT2 G-protein coupled receptors. The pleiotropic receptor-independent effects of melatonin with a possible impact on blood pressure involve the reactive oxygen species (ROS) scavenging nature, activation and over-expression of several antioxidant enzymes or their protection from oxidative damage and the ability to increase the efficiency of the mitochondrial electron transport chain. Besides the interaction with the vascular system, this indolamine may exert part of its antihypertensive action through its interaction with the central nervous system (CNS). The imbalance between the sympathetic and parasympathetic vegetative system is an important pathophysiological disorder and therapeutic target in hypertension. Melatonin is protective in CNS on several different levels: It reduces free radical burden, improves endothelial dysfunction, reduces inflammation and shifts the balance between the sympathetic and parasympathetic system in favor of the parasympathetic system. The increased level of serum melatonin observed in some types of hypertension may be a counter-regulatory adaptive mechanism against the sympathetic overstimulation. Since melatonin acts favorably on different levels of hypertension, including organ protection and with minimal side effects, it could become regularly involved in the struggle against this widespread cardiovascular pathology. PMID:25299692

Abstract Background The aim of this study is to investigate the effect of quercetin in alleviating the cytotoxic effects of Dimethoate in human peripheral blood lymphocytes. Methods Lymphocytes were divided into too groups. The first group, lymphocytes were incubated for 4 h at 37°C with different concentrations (0, 40, 60 and 100 mM) of Dimethoate. The second group was preincubated with quercetin for 30 min and followed by Dim incubation for 4 h at 37°C. ...

Abstract Background A common side effect of oxaliplatin is peripheral neurotoxicity. Oxidative stress to dorsal root ganglion (DRG) may be one of important pathogenic mechanisms. Green tea contains four polyphenol catechins, which are known to be potent antioxidants. The present work is aimed to determine whether green tea extracts have neuroproective or palliative effects on neurotoxicity symptoms induced by oxaliplatin. Methods We conducted behavioral tests in...

Commercially available Aztec marigold (Tagetes erecta) flower extract (Af.Cr) was evaluated for the in vitro antioxidant activity and in vivo analgesiceffect on acetic-acid-induced abdominal writhing. The results revealed the presence of pronounced antioxidant potential in Aztec marigold flowers and a dose-dependent (100 and 300 mg/kg) analgesiceffect. The antioxidant and analgesic activities obtained seem to be in good accordance with the medicinal uses of Aztec marigold as an anti-inflammatory and analgesic. PMID:18814202

Full Text Available The multiple traditional uses with fewer scientific investigations about C. iners bark made imperative to further exploit this plant for the evaluation of its therapeutic value. Analgesic and antioxidant activities of ethanolic, aqueous and alkaloid extracts prepared from C. iners bark was studied using both in vivo and spectrometric experimental models. Results of hot plate and tail flick studies show that all the screened extracts are devoid of central analgesic activity. However, promising findings regarding the peripheralanalgesic and anti-inflammatory activity was revealed from the formalin induced pain method with alkaloid extract possessing significant activity followed by ethanolic and aqueous extract. Moreover, the results of total phenolic content and antioxidant activity was also confirmed the presence of higher amount polyphenolic content in ethanolic extract with significant antioxidant activity. The observed peripheralanalgesic activity by ethanolic and aqueous extract might be due to the presence of higher amount polyphenolic present in them. Results of this study also supported the traditional use of this plant in the treatment of pain. Hence, it was concluded from the study that C. iners bark extract can be utilized as new source of peripheralanalgesic in the treatment of pain.

Full Text Available Experiments were carried out on outbred rabbits of both sexes using neurophysiological methods. We resurched the ability of analgesics, antidepressants and their combinations tochange parameters of electrophysiological brain activity under conditions of normal functioning of the central nervous system and on the background ofsimulated depression. Found that in brain pathology combination analgesics with amitriptyline caused activation of the reticular formation (RF and in-creased excitability of dorsomedial tonsils (DMT in comparison with its action in intact rabbits. Analysis of these data on reserpine showed the change of the sign of excitability in the frontal cortex (FC, RF (from inhibition to activation, and re-duction in the dorsal hippocampus (DH, or leveling DMT increased excitability of brain structures under the influence of this combination. Functional relationships between structures were characterized by increasing activating influence of RFon the FC and inhibiting influence of RFon DMT (increasing analgesic activity and reduce brake control DH on FC (increase antidepressant properties. Notably, the combination of celecoxib with the amitriptyline caused fewer changes in excitability of brain structures and intracentral relationships between them that assotiates with less manifested analgesic activity com-pared with the combination of" meloxicam +amitriptyline."

The reversal of the antinociceptive effect of systemically administered acetaminophen (paracetamol) by intrathecal administration of the potent 5-HT(3) receptor antagonist tropisetron has been reported in rats subjected to the paw pressure test, suggesting that acetaminophen action is mediated through spinal 5-HT(3) receptors. However, more recent data, showing differences between the pharmacological profiles of various 5-HT(3) receptor antagonists, led us to reconsider the involvement of spinal 5-HT(3) receptors. To address this question, two different approaches were used: 1) electrophysiological recordings to assess whether acetaminophen directly modulates 5-HT(3) receptor activity and 2) pharmacological investigations with various 5-HT(3) receptor antagonists and spinal 5-HT(3) receptors antisense oligodeoxynucleotides (AODNs) to determine how those treatments might affect the antinociceptive action of acetaminophen. Electrophysiological studies demonstrated that acetaminophen had no direct agonist or antagonist effects on 5-HT(3A) receptors. Unlike tropisetron, other 5-HT(3) receptor antagonists, such as ondansetron and granisetron, injected intrathecally were unable to reverse the antinociceptive effect of acetaminophen. Moreover, pretreatment with AODNs did not reverse the acetaminophen-induced antinociceptive effect, although it suppressed the antinociceptive effect of m-chlorophenylbiguanide, a specific agonist of 5-HT(3) receptors, and significantly reduced (30%) the expression of these receptors in the dorsal horn of the spinal cord. These results suggest that acetaminophen-induced antinociceptive action involves a spinal tropisetron-sensitive receptor that is not the 5-HT(3) receptor and that remains to be identified. PMID:15322266

Full Text Available The aim of this study was to evaluate the analgesic and anti-diarrheal activity of the whole plant Boerhavia repens. Sun dried roots, stems, barks and the leaves of B. repens were extracted using methanol at room temperature. The crude methanol extract was fractionated in two different solvents using Petroleum ether and Carbon Tetrachloride. The peripheralanalgesic activity was evaluated by acetic acid induced Writhing method. The petroleum ether soluble materials at a dose of 400 mg/kg exhibited significant analgesic activity with 37.05% inhibition of writhing compared to that of 50% produced by the standard diclofenac. Evaluation of central analgesic activity was carried out by tail flicking method using Morphine as a positive control. Petroleum ether soluble fraction exhibited highest central analgesic activity after 30 minutes at a dose of 400 mg/kg dose. The central analgesic activity decreased in a time dependent manner. After 90 minutes there was almost no central analgesic activity. The anti-diarrheal activity of the different fractions of the crude extract of B. repens was evaluated using the model of castor oil induced diarrhea in mice. No fractions showed significant anti-diarrheal activity.

Full Text Available The effect of methanolic extract of Pausinystalia macroceras stem-bark was investigated in chemically-induced inflammation in rodents. The extract dose-dependently (17.5-350.0 mg kg-1 inhibited acetic acid-induced writhing, formalin-induced pain licking and carrageenin-induced hind paw oedema in rodents. The extract also inhibited both the fresh egg albumin and prostaglandin E2_induced inflammations as well as capsaicin-induced nociception in rats. These inhibitions were statistically significant (p<0.01-0.001. This effect may in part involve suppression of capillary permeability through neurogenic and non-neurogenic pathways.

The use of ions to deliver radiation to a body for therapeutic purposes has the potential to be significant improvement over the use of low linear energy transfer (LET) radiation because of the improved energy deposition profile and the enhanced biological effects of ions relative to photons. Proton therapy centers exist and are being used to treat patients. In addition, the initial use of heavy ions such as carbon is promising to the point that new treatment facilities are planned. Just as with protons or heavy ions, antiprotons can be used to deliver radiation to the body in a controlled way; however antiprotons will exhibit additional energy deposition due to annihilation of the antiprotons within the body. The slowing down of antiprotons in matter is similar to that of protons except at the very end of the range beyond the Bragg peak. Gray and Kalogeropoulos estimated the additional energy deposited by heavy nuclear fragments within a few millimeters of the annihilation vertex to be approximately 30 MeV (...

In this study, we evaluated the effects of trapidil on crush injury by monitoring nitric oxide, malondialdehyde and transforming growth factor-Beta2 levels and by transmission electron microscopy in the rat sciatic nerve. The sciatic nerve was compressed for 20 sec by using a jewelers forceps. Trapidil treatment groups were administrated a single dose of trapidil (8 mg/kg intraperitoneally just after the injury. The crush and crush + trapidil treatment groups were evaluated on the 2nd, 7th, 15th, 30th and 45th days of the post-crush period. On the 7th and 15th days, damage in thin and thick myelinated axons, endoneural edema and mitochondrial swelling were less severe in the trapidil group histopathologically. These findings supported the idea that trapidil prevented cell damage and edema at the injury site. Day/group interaction with regard to serum nitric oxide, malondialdehyde and transforming growth factor-Beta2 levels did not show significant changes.

Full Text Available AbstractBackgroundPain is described as the fifth vital sign, and inadequate pain management is linked to numerous immediate and long-term negative outcomes. Venipuncture is one of the most painful medical procedures in children. Distraction is one of the main effective ways to relieve pain. Reducing patients’ pain sensation maybe feeling is important for all nurses for many reasons. Unnecessary pain can damage the nurse-patient relationship, whereas the knowledge of alternative techniques can improve patient care and satisfaction. Materials and MethodsForty patients (6–12 years suffering from thalassemia and requiring venipuncture were randomized into distraction group (n=20, regular breathing exercise and control group (n=20, without any intervention. The pediatric pain behavioral symptoms and Numeric Pain Rating Scale were used to assess pain caused by venipuncture.ResultsThe mean of pain score based on the numerical scale was 5.60 ± 3.13 in the control group and 1.85±1.42 in breathing exercises and the mean score of behavioral pain symptoms was 3.80±2.80 in the control group and 0.96±0.75 in breathing exercise group. Results showed a significant difference between the mean of pain scores (based on numeric scale and pain behavior scale. (p?0.001Conclusion Distraction demonstrated to be effective in reducing pain. This intervention requires minimum effort and time and may be a cost-effective and convenient nursing intervention that could be used easily in clinical settings.

Full Text Available The numerous reports and controlled clinical studies revealed analgesic efficacy of tricyclic antidepresants in neurogenic pain syndroms (painful diabetic neuropathy, postherpetic neuralgia, headaches, facial pain, central pain, in rheumatological disorders and in cancer pain. These clinical studies indicate an intrinsic analgesic activity of tricyclic antidepresants independent from their psychotropic effect. Such conclusions are substantiated by following findings; a significant pain relief in nondepressive patients; an analgesiceffect in healty volunteers in acute experiments; a faster onset of analgesia than antidepressant effect; the analgesic doses lower than those used for the treatment of depression. Although tricyclic antidepresants are used in the management of pain, the site and the mechanism of their analgesic action remain unclear. There has been considerable discussion at the experimental level about the nature and underlying mechanism of tricyclic antidepressant analgesia. The modulation of nociception by tricyclic antidepresants is probably centrally mediated, but the involvement of spinal and/or supraspinal structures is at present not well established. Nevertheless, in the light of current knowledges, the pain-relieving effect of the tricyclic antidepresants may involve serotoninergic, adrenergic and opioid mechanisms and may modulate various neurotransmitters (GABA, adenosine, NMDA,cholesystokinin and ion channels (Na+, K+, Ca++.

Full Text Available AIM: To evaluate the clinical effect of traditional Chinese medicine plus laser photocoagulation on eyes which have peripheral retinal hole with shallow detachment. METHODS: The 227 cases(246 eyesof retinal hole with shallow detachment were randomly divided into an integrated Chinese and western medicine group and a western medicine group. The former underwent laser photocoagulation combined with oral Chinese medicine; while the latter was treated with laser photocoagulation alone. Analyses of the effect were performed two months after treatment. RESULTS: The total cure rate of integrated Chinese and western medicine group was 87.7%, while that of western medicine group was 71.6%, significant difference was considered between the two groups(PCONCLUSION: Chinese medicine combined with laser photocoagulation plays an exact role in eyes which have peripheral retinal hole with shallow detachment, especially when the detached range is greater than 1PD, and it is significantly better than western laser therapy.

Nerve allografts are highly antigenic and require the continuous use of immunosuppressive drugs. Neurotoxic complications from immunosuppressant therapy with FK 506 have been noted in the central and peripheral nervous system although an increased rate of axonal regeneration has also been noted. Regeneration of peripheral nerve grafts was assessed in a rat model clinically and morphometrically after treatment for 2 and 6 weeks with two different doses of FK 506. Good regeneration was noted in all groups at 6 weeks. A significantly higher axon count was observed in both the FK 506 groups after 2 weeks regeneration compared with controls. This beneficial effect was not evident after 6 weeks of regeneration. Whether this is related to a pruning mechanism or to a down-regulation of regenerative processes in the nerve due to possible neurotoxic effects of FK 506 remains unknown. PMID:10190602

Full Text Available The aim of the study was to compare the analgesic activities of ethanolic extract of fruits and whole plant of Fragaria vesca in experimental animal models. The extracts were prepared by percolation method and oral toxicity testing was performed as per OECD guidelines. Analgesic activity was assessed by tail flickmethod (for central action and acetic acid-induced writhing test (for peripheral action. Fruit extract, whole plant extract and aspirin showed significant analgesic activity, both central and peripheral, as compared to control (p< 0.01. Although fruit extract at dose of 500 mg/kg showed better activity than 250 mg/kg (p<0.05. Analgesic activities of fruit extract 250 mg/kg and whole plantextract 500 mg/kg were almost equivalent while aspirin was most potent among all with significantly greater activities as compared to all the extracts (p<0.05.

Introduction: The peripheral facial paralysis (PFP) results from the reduction or interruption of the axonal transport to the seventh cranial nerve resulting in complete or partial paralysis of the facial movements. The facial deformity and limitation of movements, besides affecting the aesthetics and functionality, can significantly interfere with interpersonal communication. Objective: Investigate the psychological contents and other social effects associated to PFP in adult subjects, perfo...

Full Text Available Abstract Introduction Stress has been shown to be a tumor promoting factor. Both clinical and laboratory studies have shown that chronic stress is associated with tumor growth in several types of cancer. Corticotropin Releasing Factor (CRF is the major hypothalamic mediator of stress, but is also expressed in peripheral tissues. Earlier studies have shown that peripheral CRF affects breast cancer cell proliferation and motility. The aim of the present study was to assess the significance of peripheral CRF on tumor growth as a mediator of the response to stress in vivo. Methods For this purpose we used the 4T1 breast cancer cell line in cell culture and in vivo. Cells were treated with CRF in culture and gene specific arrays were performed to identify genes directly affected by CRF and involved in breast cancer cell growth. To assess the impact of peripheral CRF as a stress mediator in tumor growth, Balb/c mice were orthotopically injected with 4T1 cells in the mammary fat pad to induce breast tumors. Mice were subjected to repetitive immobilization stress as a model of chronic stress. To inhibit the action of CRF, the CRF antagonist antalarmin was injected intraperitoneally. Breast tissue samples were histologically analyzed and assessed for neoangiogenesis. Results Array analysis revealed among other genes that CRF induced the expression of SMAD2 and ?-catenin, genes involved in breast cancer cell proliferation and cytoskeletal changes associated with metastasis. Cell transfection and luciferase assays confirmed the role of CRF in WNT- ?-catenin signaling. CRF induced 4T1 cell proliferation and augmented the TGF-? action on proliferation confirming its impact on TGF?/SMAD2 signaling. In addition, CRF promoted actin reorganization and cell migration, suggesting a direct tumor-promoting action. Chronic stress augmented tumor growth in 4T1 breast tumor bearing mice and peripheral administration of the CRF antagonist antalarmin suppressed this effect. Moreover, antalarmin suppressed neoangiogenesis in 4T1 tumors in vivo. Conclusion This is the first report demonstrating that peripheral CRF, at least in part, mediates the tumor-promoting effects of stress and implicates CRF in SMAD2 and ?-catenin expression.

Nitrogen heterocyclic compounds such as pyrazolines have been found to possess a broad spectrum of biological activities such as anticancer, antitubercular, anti-inflammatory, analgesic, and antidepressant activities. Pyrazoline derivatives IV, V (a-e) have been synthesized from the intermediate chalcones III (a-h) by cyclizing with phenyl hydrazine and hydrazine hydrate. The structures of these compounds were confirmed by IR, NMR, and mass spectroscopy. Biological studies of the synthesized compounds showed promising antitumor, analgesic, and anti-inflammatory activities. The compounds were tested for their in vitro antitumor activity against EAC tumor cell lines. Compounds IVa and IVb showed the highest cytotoxicity of 80% at a 200 ?g mL concentration. Among the tested compounds, IVa and Vd seem to be more effectiveanalgesic agents. Compounds IVc, IVd, and Ve are found to be the most effective anti-inflammatory agents. Thus the results show that synthesized compounds possess antitumor, analgesic, and anti-inflammatory activity. It was observed that the test compounds with electron withdrawing groups (halogens) on the aromatic ring favors antitumor, analgesic, and anti-inflammatory activity. PMID:22754259

Peripheral nerve injuries are a common occurrence affecting the nerves found outside the central nervous system. Complete nerve transections necessitate surgical re-anastomosis, and, in cases where there is a significant gap between the two ends of the injured nerve, bridging strategies are required to repair the defect. The current clinical gold standard is the nerve graft, but this has a number of limitations, including donor site morbidity. An active area of research is focused on developing other techniques to replace these grafts, by creating tubular nerve-guidance conduits from natural and synthetic materials, which are often supplemented with biological cues such as growth factors and regenerative cells. In the present short review, we focus on the use of adipose-tissue-derived stem cells and the possible mechanisms through which they may exert a positive influence on peripheral nerve regeneration, thereby enabling more effective nerve repair. PMID:24849239

AbstractBackgroundPeripheral nerve blocks are effective in treating acute pain, thereby minimizing the requirement for opiate analgesics. Fractured neck of femur (FNF) is a common, painful injury. The provision of effective analgesia to this cohort is challenging but an important determinant of their functional outcome. We investigated the analgesic efficacy of continuous femoral nerve block (CFNB) in patients with FNF.MethodsFollowing institutional ethical approval and with informed consent, patients awaiting FNF surgery were randomly allocated to receive either standard opiate-based analgesia (Group 1) or a femoral perineural catheter (Group 2). Patients in Group 1 received parenteral morphine as required. Those in Group 2 received a CFNB comprising a bolus of local anaesthetic followed by a continuous infusion of 0.25% bupivacaine. For both Groups, rescue analgesia consisted of intramuscular morphine as required and all patients received paracetamol regularly. Pain was assessed using a visual analogue scale at rest and during passive movement (dynamic pain score) at 30?min following first analgesic intervention and six hourly thereafter for 72 hours. Patient satisfaction with the analgesic regimen received was recorded using verbal rating scores (0-10). The primary outcome measured was dynamic pain score from initial analgesic intervention to 72 hours later.ResultsOf 27 recruited, 24 patients successfully completed the study protocol and underwent per protocol analysis. The intervals from recruitment to the study until surgery were similar in both groups [31.4(17.7) vs 27.5(14.2) h, P?=?0.57]. The groups were similar in terms of baseline clinical characteristics. For patients in Group 2, pain scores at rest were less than those reported by patients in Group 1 [9.5(9.4) vs 31(28), P?=?0.031]. Dynamic pain scores reported by patients in Group 2 were less at each time point from 30?min up to 54 hours [e.g at 6?h 30.7(23.4) vs 67.0(32.0), P?=?0.004]. Cumulative morphine consumption over 72?h was less in Group 2. Patient satisfaction scores were greater in Group 2 [9.4(1.1) vs 7.6(1.8), P?=?0.014].ConclusionsCFNB provides more effective perioperative analgesia than a standard opiate-based regimen for patients undergoing fixation of FNF. It is associated with lesser opiate use and greater patient satisfaction.

Full Text Available Abstract Background Peripheral nerve blocks are effective in treating acute pain, thereby minimizing the requirement for opiate analgesics. Fractured neck of femur (FNF is a common, painful injury. The provision of effective analgesia to this cohort is challenging but an important determinant of their functional outcome. We investigated the analgesic efficacy of continuous femoral nerve block (CFNB in patients with FNF. Methods Following institutional ethical approval and with informed consent, patients awaiting FNF surgery were randomly allocated to receive either standard opiate-based analgesia (Group 1 or a femoral perineural catheter (Group 2. Patients in Group 1 received parenteral morphine as required. Those in Group 2 received a CFNB comprising a bolus of local anaesthetic followed by a continuous infusion of 0.25% bupivacaine. For both Groups, rescue analgesia consisted of intramuscular morphine as required and all patients received paracetamol regularly. Pain was assessed using a visual analogue scale at rest and during passive movement (dynamic pain score at 30?min following first analgesic intervention and six hourly thereafter for 72 hours. Patient satisfaction with the analgesic regimen received was recorded using verbal rating scores (0-10. The primary outcome measured was dynamic pain score from initial analgesic intervention to 72 hours later. Results Of 27 recruited, 24 patients successfully completed the study protocol and underwent per protocol analysis. The intervals from recruitment to the study until surgery were similar in both groups [31.4(17.7 vs 27.5(14.2 h, P?=?0.57]. The groups were similar in terms of baseline clinical characteristics. For patients in Group 2, pain scores at rest were less than those reported by patients in Group 1 [9.5(9.4 vs 31(28, P?=?0.031]. Dynamic pain scores reported by patients in Group 2 were less at each time point from 30?min up to 54 hours [e.g at 6?h 30.7(23.4 vs 67.0(32.0, P?=?0.004]. Cumulative morphine consumption over 72?h was less in Group 2. Patient satisfaction scores were greater in Group 2 [9.4(1.1 vs 7.6(1.8, P?=?0.014]. Conclusions CFNB provides more effective perioperative analgesia than a standard opiate-based regimen for patients undergoing fixation of FNF. It is associated with lesser opiate use and greater patient satisfaction.

The spectrum of distribution of the rat peripheral blood erythrocytes alters during adaptation to altitude-induced hypoxia as well as under the effects of increasing concentrations of the serum lipid constituents, arterial and venous plasma factors of animals initially adapted to hypoxia, and that of 2,3-DPG. The pattern of erythrocyte distribution in the periphery seems to depend on the micromedium conditions created by organ metabolic specifics, as well as on erythrocyte intracellular factors, there- by optimizing the system of oxygen supply to organs and tissues. PMID:2759288

The effect of radiation on human peripheral blood T-lymphocytes and their subpopulations was studied. With E rosette formation and nonspecific esterase staining (ANAE) methods, we have detected the kinetic changes of percentage of E rosette ormation and ANAE activity in the peripheral blood lymphocytes of 15 healthy male adults who were exposed to 60Co ?-ray 25 to 800 rads and incubated in vitro for 2 and 18 hours. And by using EAG(Tr) and EAM(Tu) rosette forming assay, we have estimated the kinetic changes of the percentages of Tr and Tu cells at 24 and 48 hours after incubation following graded doses of ?-ray irradiation (100 to 1600 rad) to the peripheral T-lymphocytes of 10 healthy male adults. The results were as follows: (1) Ionizing radiation had a significant inhibitory effect on the ability of E rosette formation and ANAE activity of T-cells, and showed dose- and time-related reductions. Moreover, the stronger inhibition of ANAE activity seemed to be related to the higher sensitivity of T-lymphocytes to impairment. (2) Their dose-response curves were biphasic, and the D0 values of radiosensitive and radioresistant components of ERFC and ANAE were calculated, which suggested that there would be several subpopulations with different radiosensitivity in T-lymphocytes. (3) The decrease in percentage of EAG-RFC was more remarkable as compared with those of EAM-RFC, either 24 or 48 hours after irradiation; therefore, Tr cells are more radiosion; therefore, Tr cells are more radiosensitive than Tu cells

Neuroprotective effect of Ginkgo biloba extract EGb761 in cisplatin (cis-diamminedi-chloroplatinum, or CDDP)-induced peripheral neuropathy was investigated. Swiss albino mice were treated with CDDP, 2 mg/kg ip twice a week for nine times. One group of the animals also received EGb761 in the drinking water at an estimated dosage of 100 mg/kg per day. Two other groups received vehicle (control) or EGb761 only. Development of neuropathy was evaluated with changes in sensory nerve conduction velocity (NCV). Following the treatments, dorsal root ganglia (DRGs) were microscopically examined and some were cultured for 3 days. EGb761 proved effective in preventing the reduction in NCV (P < 0.0001) caused by CDDP. CDDP caused a decrease in the number of migrating cells (P < 0.01) and in the length of outgrowing axons (P < 0.01) while EGb761 treatment prevented the latter. CDDP led to smaller nuclear and somatic sizes in neurons (P < 0.01), while with EGb761 co-administration, both were close to control values. Animals having EGb761 only had similar results with controls. In conclusion, EGb761 was found to be effective in preventing some functional and morphological deteriorations in CDDP-induced peripheral neuropathy

Objective: To determine how the vasodilator glyceryl trinitrate (GTN) alters arterial stiffness and improves left ventricular afterload. Methods: Ascending aortic pressure waves were measured with fluid filled catheters of high fidelity in 50 patients undergoing cardiac surgery, before cardiopulmonary bypass, both before and after intravenous infusion of GTN. In all 50 patients, wave reflection was identifiable as a secondary boost to late systolic pressure, permitting the pressure wave to be separated into a primary component, attributable to left ventricular ejection and properties of the proximal aorta, and a secondary component, attributable to reflection of the primary wave from the peripheral vasculature. Results: GTN infusion caused no change in amplitude of the primary wave (mean (SD) 0.0 (1.4) mm Hg, not significant) but substantial reduction (14.6 (9.6) mm Hg, p < 0.0001) in amplitude of the secondary reflected wave. Fall in mean pressure was attributable to a mix of arteriolar and venous dilatation, with relative contributions unable to be separated. Conclusion: Favourable effects of GTN on arterial stiffness can be attributed to effects on peripheral muscular arteries, causing reduction in wave reflection. Results conform with previous invasive studies on vasodilator agents and their known effects on calibre and compliance of muscular arteries. PMID:15761047

Full Text Available The purpose of this study was to investigate the effects of a traditional Japanese medicine Goshajinkigan (TJ-107 and Tokishigyakukagoshuyushokyoto (TJ-38 on warm sense threshold, cold sense threshold and the peripheral blood flow. 31 healthy volunteers (control group: 9people, TJ-107 group: 12 people, TJ-38group:10 people were examined. Drugs administered 2.5 g a dose. Analysis was before and after 1 hour dosage. The warm and cold sense threshold in the thenar of the non-handedness site of these subjects was measured using a thermostimulator (Intercross-200, Intercross Co., Tokyo, Japan. The peripheral blood flow in the finger of the non-handedness site of these subjects was measured using a full-field laser perfusion imager (FLPI, Moor Instruments Ltd., England. Control: The vehicle had no significant effect on the warm sense threshold, cold sense threshold and the peripheral blood flow. TJ-107: The warm sense threshold and cold sense threshold were significantly decreased, and the reaction latency of cold sense was significantly shortening. The peripheral blood flow was significantly increased second and third finger at 115.6%, 119.3%, respectively. TJ-38: The cold sense threshold and the reaction latency of cold sense were significantly increased. The peripheral blood flow was significantly increased second and third finger with 114.3%, 112.8%, respectively. These results suggest that TJ-107 and TJ-38 have effects on the changed warm sense threshold, cold sense threshold and increased peripheral blood flow.

Neurofibromatosis type 1 (NF1) is an inherited genetic disease affecting 1 in 3,500 individuals. A prominent feature of NF1 is the formation of benign tumours of the peripheral nerve sheath (neurofibromas). However, these can become malignant and form highly metastatic malignant peripheral nerve sheath tumours (MPNST), which are usually fatal despite aggressive surgery, chemotherapy, and radiotherapy. Recent studies have shown that pigment epithelium-derived factor (PEDF) can induce differentiation and inhibit angiogenesis in several kinds of tumours. The present study was designed to determine the in vitro and in vivo effects of PEDF on MPNST angiogenesis and tumour growth. PEDF inhibited proliferation and augmented apoptosis in S462 MPNST cells after 48 h of treatment in culture. In xenografts of S462 MPNST cells in athymic nude mice, PEDF suppressed MPNST tumour burden, due mainly to inhibition of angiogenesis. These results demonstrate for the first time inhibitory effects of PEDF on the growth of human MPNST via induction of anti-angiogenesis and apoptosis. Our results suggest that PEDF could be a novel approach for future therapeutic purposes against MPNST. PMID:24078214

The protective effect of YM-254890, a specific Galphaq/11 inhibitor, on laurate-induced peripheral arterial disease in rats was compared with those of prostaglandin E1 (PGE1), beraprost, and clopidogrel. YM-254890 inhibited ADP-induced ex vivo rat platelet aggregation at a dose of 3 microg/kg. Furthermore, YM-254890 strongly inhibited phenylephrine-, serotonin- and endothelin-1-induced contractions in the rat aorta, and improved dermal blood flow after the laurate injection. The intra-arterial single bolus administration of YM-254890 15 min after the laurate injection dose-dependently inhibited the progression of the lesion, with significance, at 3 microg/kg without affecting systemic blood pressure. PGE1 and beraprost, when administered before the laurate injection, were effective, but their potencies were less than that of YM-254890. Clopidogrel significantly suppressed lesion progression when administered at 30 mg/kg twice a day for 3 days, which completely inhibited platelet aggregation. These results suggest that the local administration of YM-254890 may be useful for treating peripheral arterial disease. PMID:16566917

The semi-classical Landau Vlasov model has been used to investigate the decay modes of peripheral Pb + Au reactions at 29 MeV/n. Statics and dynamics of these very massive nuclei are analyzed especially through the isospin dependence of the effective nuclear force. The degree of dissipation of the collisions is studied for different bins of impact parameter pointing out the influence of the nucleon-nucleon cross section. The appearance of intermediate mass fragments from neck-like structures is evidenced and the effects of angular momentum transfers are shown to play a fundamental role in this phenomenon. The theoretical results are compared with experimental data, showing the importance of the dynamical and out of equilibrium effects on the observables. (authors)

Earlier reviews have covered pharmacokinetic drug interactions of natural and semi-synthetic opioid analgesics. This review will focus on the pharmacokinetic drug-drug interactions of methadone, propoxyphene, levomethadyl, meperidine, other phenylpiperidines (such as fentanyl), pentazocine, diphenoxylate, loperimide, and tramadol. The authors present an extensive review of the current literature. These drugs, with a few exceptions, are, at least partially, if not primarily, metabolized by the cytochrome P450 isoenzyme system (CYP) 3A4, and the action/interaction of these enzymes can have an effect on outcome. Therefore, these drugs are likely to produce drug-drug interactions when the CYP3A4 system is inhibited or induced. Knowledge of these drug-drug interactions is important because such interactions may decrease drug efficacy or result in adverse effects. PMID:19377028

Dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2; DM) and its analogs obtained via stereochemical transformation of L-Pro6 to D-Pro6 peptide in DM ([Dpro6]DM) and via dehydration of L-Pro6 peptide ([dHPro6]DM) were characterized with respect to the analgesic activity in rats tested under conditions corresponding to various levels of pain sensitivity organization. The drugs were introduced by intraperitoneal injections in various doses (0.1, 1.0, and 10 mg/kg). In the case of acetic-acid induced convulsions (writhing), DM and [Dpro6]DM produced analgesic action in the minimum dose, while the analogous effect of [dHPro6]DM was observed only in greater doses. In the tail-clamp (Haffner) test, DM and [Dpro6]DM also inhibited nociception while the latter compound was ineffective. In the grid-shock test, [Dpro6]DM showed a higher activity than [dHPro6]DM, whereas DM did not produce analgesic action. Thus, all the studied peptides exhibit pronounced analgesic activity, and the replacement of L-Pro6 in DM by its stereomer D-Pro is more effective than the substitution of dHPro6. PMID:15934358

The aim of the study is to establish whether or not acquired in phagocytic activity occur in breast carcinoma patients (BCP) undergoing radiotherapy (RT). Using flowcytometer, assessment is done of lymphocyte phagocytosis (LP) and respiratory burst activity (RBA) of peripheral monocyte (Mo) and neutrophil granulocytes (Gr) in a series of 15 BCP, presenting clinical and laboratory characteristics, as follows: diagnosis - mammary gland carcinoma (stage I and IIa) age 42±10 y, successful radical mastectomy, radiotherapy (RT) course 21 days with fractionated gamma irradiation 2Gy daily over 3 weeks (total dose 40 Gy), frequency of check-up examinations - three times: before (BCP-1), at 7 (BCP-2) and 21 (BCP-3) days in the course of RT. Fifteen clinically healthy persons, aged 34-45 years are used for control purposes. Before RT impairment of basal phagocytic and oxidizing activity in Mo and Gr is recorded. Later on 7 days of RT, phagocytic cells become 'primed' and generate increased H2O2 amounts. At termination of the study RBA reduction relative to a variety of stimulants along with reduced phagocytosis are noted. Flowcytometric assessment of phagocytes yields prompt and adequate information about the postirradiation effects on peripheral leukocytes. The results described may prove helpful to radiologists and immunologists with a view to opportune detection of phagocytic dysfunction in immunocompromised patientsients

Pyrethroids such as permethrin are synthetic compounds widely used in the agriculture of many countries to combat plagues and in domestic products, such as acaricides. Not so long ago these chemicals were characterized as non-toxic for non-target organisms; however, recent studies have showed that these compounds could present toxic potential for many organisms. In this sense, this study presents genotoxic and mutagenic potential of permethrin administered intraperitoneally in mice under artificial conditions by the use of micronucleus assay in the peripheral blood of these animals. The mice were divided into five groups: group I = negative control (distilled water), group II = positive control (cyclophosphamide), group III = 30% of permethrin LD(50) (96 mg/kg), group IV = 50% of permethrin LD(50) (160 mg/kg), and group V = 80% of permethrin LD(50) (256 mg/kg). The peripheral blood was collected 24, 48, and 72 h after treatment. Results showed that all the tested permethrin dosages presented genotoxic and mutagenic effects 24 h after treatment, which would contradict the classification of this chemical product as moderately toxic, i.e., unable to cause damages to the cell DNA. PMID:22965619

The purpose of this study was to determine the extent of peripheral visual deficits in patients with early age-related macular degeneration (ARMD) using electrophysiological and psychophysical techniques. Dark-adaptation curves, electro-oculograms (EOGs), and electroretinograms (ERGs) were obtained from patients with early ARMD and from normally sighted control subjects. The control subjects' data were used to calculate age-dependent 95% confidence intervals for each measure of visual function. For the control subjects, performance on all our measures of visual function decreased with age. For the patients with early ARMD, the cone system absolute thresholds, EOG ratios, and cone-dominated ERG amplitudes and implicit times were within the range of normal age-related changes. Rod system absolute thresholds, cone-rod break times, and rod-dominated electroretinographic measures were abnormal in some patients. These results suggest that when the effects of aging are taken into account, some patients classified as early ARMD may not show significant changes in peripheral retinal function with standard clinical tests. PMID:9159805

Full Text Available Objectives ?To investigate the adverse effect of manganese exposure on the iron metabolism in peripheral blood of professionally exposed workers. Methods ?The manganese in air was collected using personal air sampler, and the time weighted average (TWA concentration of exposure to manganese was then calculated. The subjects were divided into exposure group (n=85 and control group (n=80 based on the exposure doses they received. The concentrations of iron and manganese in the plasma and blood cells of the subjects were determined using flame atomic absorption detector and graphite furnace atomic absorption detector. Serum ferritin, transferrin, transferrin receptor and total iron binding capacity were determined using enzyme linked immunosorbent assay. Results ?The manganese contents in both plasma and blood cells were much higher in exposure group than in control group (P 0.05. It was revealed by linear correlation analysis that no linear correlation existed between the professional exposure time and manganese and iron contents in both plasma and blood cells, serum ferrin, transferrin, transferring receptor and total iron binding capacity (P>0.05. Conclusion ?The long-term exposure to high dose manganese may result in an imbalance of iron metabolism in the peripheral blood in exposed population, manifesting a decrease of plasma iron and serum transferrin receptors, and an increase of serum transferrin.

The effects of recombinant human interleukin-6 (rhIL-6) on the recovery of peripheral blood picture in 6.5 Gy ?-ray irradiated (132-127.7 R/min)C57BL/6J mice at the age of 80-90 days were studied. Group 1 served as the control and groups 2-5 were injected subcutaneously with rhIL-6 twice daily at doses of 10,200,500 and 1000 ?g-1kg-1d-1, respectively, starting from 30 min after irradiation for 4 consecutive days. Peripheral WBC, RBC, and PLT counts, hemoglobin and hematocrit were determined before and 5,11,14,18,22 and 30 days after irradiation. It was shown that although the time of nadir emergence and the onset of recovery were similar in all the five groups, the nadir values were higher and the recovery was better, both being dose-dependent, in the IL-6 treated groups than in the control. Significant dose-response regression equations were obtained for WBC count on day 22, for RBC count on days 14 and 18, for PLT count on days 11 and 18. Our studies show that IL-6 is a candidate of thrombopoietic factor for treatment of radiation-induced thrombocytopenia

In the present study, 70% ethanol extract of Mimusops elengi Linn. bark was assessed for antiinflammatory, analgesic and antipyretic activities in animals. The antiinflammatory activity of ethanol extract of Mimusops elengi (200 mg/kg, p.o) was evaluated using carrageenan-induced paw edema and cotton pellet-induced granuloma models. Analgesiceffect was evaluated using acetic acid-induced writhing and Eddy's hot plate models and antipyretic activity was assessed by Brewer's yeast-induced pyrexia in rats. The ethanol extract of Mimusops elengi (200 mg/kg, p.o) significantly inhibited the carrageenan-induced paw oedema at 3rd and 4th h and in cotton pellet model it reduced the transudative weight and little extent of granuloma weight. In analgesic models the ethanol extract of Mimusops elengi decreases the acetic acid-induced writhing and it also reduces the rectal temperature in Brewer's yeast induced pyrexia. However, Mimusops elengi did not increase the latency time in the hot plate test. These results show that ethanol extract of Mimusops elengi has an antiinflammatory, analgesic and antipyretic activity. PMID:21218059

Full Text Available In the present study, 70% ethanol extract of Mimusops elengi Linn. bark was assessed for antiinflammatory, analgesic and antipyretic activities in animals. The antiinflammatory activity of ethanol extract of Mimusops elengi (200 mg/kg, p.o was evaluated using carrageenan-induced paw edema and cotton pellet-induced granuloma models. Analgesiceffect was evaluated using acetic acid-induced writhing and Eddy?s hot plate models and antipyretic activity was assessed by Brewer?s yeast-induced pyrexia in rats. The ethanol extract of Mimusops elengi (200 mg/kg, p.o significantly inhibited the carrageenan-induced paw oedema at 3rd and 4th h and in cotton pellet model it reduced the transudative weight and little extent of granuloma weight. In analgesic models the ethanol extract of Mimusops elengi decreases the acetic acid-induced writhing and it also reduces the rectal temperature in Brewer?s yeast induced pyrexia. However, Mimusops elengi did not increase the latency time in the hot plate test. These results show that ethanol extract of Mimusops elengi has an antiinflammatory, analgesic and antipyretic activity.

Full Text Available Objective: To study analgesic and anti-inflammatory activities of a methanolic extract (ME of Argyreia speciosa (AS root powder. Materials and Methods: The study was carried out using male albino mice (20-25 gm and male wistar rats (100-150gm. The ME was prepared using soxhlet extraction process. The effect of ME of A. speciosa was investigated for analgesic activity using acetic acid-induced abdominal constriction, tail immersion method and hot plate method. The anti-inflammatory activity of ME of AS roots was studied using carrageenan-induced rat paw edema. Result: The ME of A. speciosa root was used in pain and inflammation models. The analgesic activity of AS at the dose of (30,100, and 300 mg/kg p.o showed significant (P< 0.01 decrease in acetic acid-induced writhing, whereas ME of A. speciosa at the dose of (100, 300 mg/kg p.o showed significant (P< 0.01 increase in latency to tail flick in tail immersion method and elevated mean basal reaction time in hot plate method. The ME of the A. speciosa at doses (30, 100, and 300mg/kg showed significant (P < 0.01 inhibition of carrageenan induced hind paw edema in rats. Conclusion: The ME of A. speciosa showed significant analgesic and anti-inflammatory activity in mice and rat.

This study deals with the antiulcer effect of water extract and ether extract of Cinnamomum cassia on four types of experimental gastric ulcer and with the antidiarrhea effect on two types of medicine-induced diarrhea in mice. These extracts have choleretic effect in anesthetized rats, and are analgesic as well. This is the pharmacologic basis of spleen-stomach warming and analgesic action of Cinnamomum cassia. PMID:8011112

Bimoclomol (BML), a symptomatic antidiabetic agent, has been developed by Biorex R & D Co. to treat diabetic neuropathy and retinopathy. BRX-220, an orally active member of the BRX family, has been developed to treat diabetic complications and insulin resistance (IR) as a follow-up compound. The effect of BRX-220 on peripheral neuropathy was examined in rats with diabetes (type 1) induced by administration of a beta-cell toxin, streptozotocin (STZ, 45 mg/kg iv). Nerve functions were evaluated by electrophysiological measurements of muscle motor and sensory nerve conduction velocities (MNCV and SNCV, respectively). MNCV and SNCV decreased in diabetic rats by 25% (p Insulin sensitivity was measured using the insulin tolerance test (ITT), both in STZ diabetic and in Zucker diabetic fatty (ZDF) rats (model of type 2 diabetes). Severe IR was detected in STZ diabetic and ZDF rats. This resistance was significantly (p < 0.05) reduced by BRX-220 treatment. PMID:12079878

We created a computational optical model of spherical fish lenses that takes into account the effects of the peripheral layers, which differ in cellular composition from the bulk of the lens. A constant refractive index, except for the lens capsule, in the outer about 6% of lens radius made it possible to uniquely infer the refractive index gradient in more central layers from a known or desired longitudinal spherical aberration curve using the inverse Abel transform. Since the zone of constant refractive index is wider than necessary to make the solution unique and for optimal optical performance of the lens, we propose that its width be set by the metabolic needs of the lens. PMID:18830325

Sympathetic nervous activity (SNA) in the liver, heart, pancreas and interscapular brown adipose tissue was examined 60 min after the third cerebroventricular injection of neostigmine (5 x 10(-8) mol) in rats. We employed the technique of specific gas chromatography-mass spectrometry for simultaneous analysis of norepinephrine (NE) and its primary neuronal metabolite, 3,4-dihydroxyphenylethyleneglycol (DHPG) and used the ratio DHPG/NE as an index of SNA. Neostigmine produced significant increases in the DHPG/NE ratio in all tissues investigated. Co-administration of atropine with neostigmine completely inhibited this neostigmine-induced effect. These findings suggest that the central cholinergic-muscarinic activation with neostigmine stimulates SNA in the peripheral tissues examined. PMID:1868343

Curcumin has shown a wide range of properties such as anti-inflammatory and anti-carcinogenic properties. Many of these effects, mainly the anti-carcinogenic effect, could be linked to its anti-oxidant effects. Nevertheless, some studies suggest that this natural compound possesses both pro- and anti-oxidative effects and that curcumin could be a genotoxic agent for some cell lines. We evaluated the genetic damage induced by curcumin to human lymphocytes exposed to increasing concentrations (0-50 ?g/ml) of curcumin. Biomarkers such as chromosome aberrations (CAs) and sister chromatid exchange (SCE) were analyzed. In addition to the cytogenetic analysis, the effect of curcumin in the cell proliferation kinetics (CPK) by the proliferation index (PI) was also analyzed. The results indicated that high concentrations of curcumin induced CAs, mainly acentric fragments. SCEs rate was not statistically different from the control group in any curcumin treated cell group. The PI of cells treated with 2 and 5 ?g/ml of curcumin were statistically significant from the control group and finally, the MI showed a tendency to increase in all the concentrations of curcumin tested. In conclusion, it can be assumed that the higher concentrations of curcumin evaluated have a cyto and genotoxic effect, in vitro, for human peripheral lymphocytes. PMID:22713711

Our project aimed to investigate the effects of mercury on the proliferation of human peripheral lymphocytes in vitro. The lymphocytes were isolated from the blood collected from healthy donors at Regionalne Centrum Krwiodawstwa i Krwiolecznictwa in Poznan, Poland. For the purpose of cell culture, the lymphocyte suspension (25 · 104 cells/ml) in Eagle's medium supplemented with 10% fetal calf serum was prepared. Phytohaemagglutinin-L (PHA-L) was used in a concentration of 2.5 mg/ml to stimulate cell proliferation. Mercuric chloride (HgCl2) in four different concentrations (1 ?M, 10 ?M, 50 ?M, 100 ?M) and [3H]-thymidine were added after 48 hours of incubation and the cell culture was continued for the next 24 hours. The rate of lymphocyte proliferation was measured by [3H]-thymidine incorporation method with a liquid scintillation counter. Results indicate that higher concentrations of mercury (50 ?M, 100 ?M) inhibit the [3H]-thymidine incorporation of human peripheral lymphocytes in vitro. The incorporation was lower than the control sample by 65% at a concentration of 50 ?M, while at a concentration of 100 ?M it fell to virtually zero. Moreover, the phase of lymphocyte proliferation cycle affected by mercuric chloride was also investigated. For this purpose HgCl2 in 2 concentrations (10 ?M, 50 ?M) was added to the cell culture in 4 different time points: at the start of the cell culture and after 4, 24, and 48 hours of incuter 4, 24, and 48 hours of incubation. After 48 hours, [3H]-thymidine was added and the cell culture was continued for an additional 24 hours. The rate of cell proliferation was estimated by [3H]-thymidine incorporation using a liquid scintillation counter. The inhibition effect was observed in samples with metal added at the start of the cell culture and after 4 h of incubation, i.e. at the initial phase of the lymphocyte proliferation cycle. (authors)

Full Text Available Abstract Background A common side effect of oxaliplatin is peripheral neurotoxicity. Oxidative stress to dorsal root ganglion (DRG may be one of important pathogenic mechanisms. Green tea contains four polyphenol catechins, which are known to be potent antioxidants. The present work is aimed to determine whether green tea extracts have neuroproective or palliative effects on neurotoxicity symptoms induced by oxaliplatin. Methods We conducted behavioral tests including sensory and thermal thresholds, an electrophysiological study, and TUNEL staining to assess neurotoxicity during the experimental period using animal models. Results A total of 14 adult rats were randomly allocated into two groups. Oxaliplatin (4?mg/kg with or without green tea (300?mg/kg orally once daily was administered intraperitoneally twice per week for 6?weeks. At 4 and 6?weeks after oxaliplatin administration, sensory threshold values were significantly decreased and at 6?weeks after oxaliplatin administration, thermal threshold values were significantly increased in oxaliplatin-treated rats compared with those in rat treated with oxaliplatin and green tea extracts. The electrophysiological assessment, including sensory nerve conduction and H-reflex-related sensory nerve conduction velocity, revealed no significant changes in the two groups. TUNEL staining showed no significant difference in the number of apoptotic-featured cells between the two experimental groups in the DRG or peripheral nerves, but the number of apoptotic-featured cells in DRG was higher than that in sciatic nerves within each group. Conclusions Green tea extracts may be a useful adjuvant to alleviate sensory symptoms after oxaliplatin administration, such as allodynia, but did not prevent morphometric or electrophysiological alterations induced by oxaliplatin.

The anti-inflammatory and analgesiceffects of theacrine (1, 3, 7, 9-tetramethyluric acid), a purine alkaloid which is abundantly present in Camellia kucha, were investigated. Xylene-induced ear edema, acetic acid-induced vascular permeability and lambda-carrageenan-induced paw edema were used to investigate anti-inflammatory activity, and acetic acid-induced writhing and hot-plate tests were used to determine analgesiceffect. Oral administration of theacrine (8-32 mg/kg) induced dose-related anti-inflammatory and analgesiceffects. On the other hand, oral caffeine administration (8-32 mg/kg) did not show an inhibitory effect on the inhibition of inflammatory response or cause analgesia. Additionally, the result of the acute toxicity test showed that the LD(50) of theacrine was 810.6 mg/kg (769.5-858.0mg/kg). The data obtained suggest theacrine possessed analgesic and anti-inflammatory activities. PMID:20227468

Full Text Available Chemotherapy induced peripheral neuropathy (CIPN is a type of neuropathic pain that is a major dose-limiting side-effect of potentially curative cancer chemotherapy treatment regimens that develops in a ‘stocking and glove’ distribution. When pain is severe, a change to less effective chemotherapy agents may be required, or patients may choose to discontinue treatment. Medications used to alleviate CIPN often lack efficacy and/or have unacceptable side-effects. Hence the unmet medical need for novel analgesics for relief of this painful condition has driven establishment of rodent models of CIPN. New insights on the pathobiology of CIPN gained using these models are discussed in this review. These include mitochondrial dysfunction and oxidative stress that are implicated as key mechanisms in the development of CIPN. Associated structural changes in peripheral nerves include neuronopathy, axonopathy and/or myelinopathy, especially intra-epidermal nerve fiber (IENF degeneration. In patients with CIPN, loss of heat sensitivity is a hallmark symptom due to preferential damage to myelinated primary afferent sensory nerve fibers in the presence or absence of demyelination. The pathobiology of CIPN is complex as cancer chemotherapy treatment regimens frequently involve drug combinations. Adding to this complexity, there are also subtle differences in the pathobiological consequences of commonly used cancer chemotherapy drugs, viz platinum compounds, taxanes, vincristine, bortezomib, thalidomide and ixabepilone, on peripheral nerves.

In this review, the first of two parts, we first provide an overview of the orthodox analgesics used commonly against cancer pain. Then, we examine in more detail the emerging evidence for the potential impact of analgesic use on cancer risk and disease progression. Increasing findings suggest that long-term use of nonsteroidal anti-inflammatory drugs, particularly aspirin, may reduce cancer occurrence. However, acetaminophen may raise the risk of some hematological malignancies. Drugs acting upon receptors of gamma-aminobutyric acid (GABA) and GABA "mimetics" (eg, gabapentin) appear generally safe for cancer patients, but there is some evidence of potential carcinogenicity. Some barbiturates appear to slightly raise cancer risks and can affect cancer cell behavior in vitro. For cannabis, studies suggest an increased risk of squamous cell carcinoma of the tongue, larynx, and possibly lung. Morphine may stimulate human microvascular endothelial cell proliferation and angiogenesis; it is not clear whether this might cause harm or produce benefit. The opioid, fentanyl, may promote growth in some tumor cell lines. Opium itself is an emerging risk factor for gastric adenocarcinoma and possibly cancers of the esophagus, bladder, larynx, and lung. It is concluded that analgesics currently prescribed for cancer pain can significantly affect the cancer process itself. More futuristically, several ion channels are being targeted with novel analgesics, but many of these are also involved in primary and/or secondary tumorigenesis. Further studies are needed to elucidate possible cellular and molecular effects of orthodox analgesics and their possible long-term impact, both positive and negative, and thus enable the best possible clinical gain for cancer patients. PMID:24470767

The experiments with unrestrained cats showed that opioid analgesics in near-analgesic doses decreased the amplitude of the primary test response recorded in the second sensorimotor zone of the cerebral cortex in 20-150-msec interval between the stimuli applied to thalamocortical fibers radiating from thalamic n. VPL. Application of test substances affecting certain neurotransmitter processes and microionophoretic application of drugs and neurotransmitters to cortical neurons showed that the inhibitory effect of opioid analgesics on cerebral cortex is probably realized through GABA-, serotonin-, beta-adreno-, and cholinergic structures. The excitatory amino acids are also involved into this process. PMID:11687833

Peripheral dynamic movements are used as part of postoperative protocols and for preventing vascular complications during bed rest. The effects of peripheral movements have not been studied. The purposes of these studies were to explain the effects of peripheral dynamic movements on lower limb circulation. The aim was also to explain how other factors like sex, age, BMI, medication, smoking, sports activity etc. affect the circulation. Healthy young subjects (N=19), healthy elderly subjects (N=19) and diabetic subjects (N=21) participated in the studies between 1997 and 1999. The study design was the same in each study. Infrared technology and image processing belong to our focus fields of applied research and IR is widely used in our real time industrial applications including also ongoing research of new possibilities. This paper presents the results of our newest application of IR thermography, where it was used to measure the skin temperature over the soleus muscle during and after dynamic ankle movements. The results showed that the skin temperature increased further during the recovery period after movements, and temperature was highest after 3- 5 minutes. Diabetic male subjects were the only subgroup that had immediate decrease during recovery period. The studies showed that smoking had a negative effect on circulation. BMI had also negative correlation (-0,356), showing that subjects with higher BMI had less increase. The results proved that peripheral movements were effective for increasing circulation in the soleus muscle and the effect was still seen after 15 minutes.

Full Text Available Abstract Background One of the genes suggested to play an important role in the pathophysiology of bipolar disorder (BPD is PDLIM5, which encodes LIM domain protein. Our main objective was to examine the effect of olanzapine treatment on PDLIM5 mRNA expression in the peripheral blood leukocytes of BPD patients. Methods We measured the expression of PDLIM5 mRNA from 16 patients with BPD Type I after 0, 4, and 8 weeks of treatment with olanzapine using quantitative real-time PCR. The Young Mania Rating Scale was used to evaluate the severity of manic symptoms in BPD patients. We also compared PDLIM5 mRNA expression in treatment-naïve BPD patients with that in healthy control subjects. Results No significant difference was found in PDLIM5 mRNA expression between patients before olanzapine treatment and following 4 and 8 weeks of treatment (p>0.05. Although we observed a significant reduction in the severity of manic symptoms in all BPD patients (pPDLIM5 mRNA (p>0.05. Interestingly, PDLIM5 mRNA expression differed significantly between treatment-naïve BPD patients and healthy control subjects (p=0.002. Conclusion PDLIM5 mRNA expression did not appear to be a reflection of the efficacy of olanzapine in reducing the manic symptoms of BPD. The significant difference in expression of PDLIM5 mRNA in the peripheral blood leukocytes of treatment-naïve BPD patients versus that of healthy control subjects, however, suggests that it may be a good biological marker for BPD.

The use of early corticosteroid withdrawal (ECSW) protocols after kidney transplantation has become common, but the effects on fracture risk and bone quality are unclear. We enrolled 47 first-time adult transplant recipients managed with ECSW into a 1-year study to evaluate changes in bone mass, microarchitecture, biomechanical competence, and remodeling with dual energy x-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT), parathyroid hormone (PTH) levels, and bone turnover markers obtained at baseline and 3, 6, and 12 months post-transplantation. Compared with baseline, 12-month areal bone mineral density by DXA did not change significantly at the spine and hip, but it declined significantly at the 1/3 and ultradistal radii (2.2% and 2.9%, respectively; both P<0.001). HRpQCT of the distal radius revealed declines in cortical area, density, and thickness (3.9%, 2.1%, and 3.1%, respectively; all P<0.001), trabecular density (4.4%; P<0.001), and stiffness and failure load (3.1% and 3.5%, respectively; both P<0.05). Findings were similar at the tibia. Increasing severity of hyperparathyroidism was associated with increased cortical losses. However, loss of trabecular bone and bone strength were most severe at the lowest and highest PTH levels. In summary, ECSW was associated with preservation of bone mineral density at the central skeleton; however, it was also associated with progressive declines in cortical and trabecular bone density at the peripheral skeleton. Cortical decreases related directly to PTH levels, whereas the relationship between PTH and trabecular bone decreases was bimodal. Studies are needed to determine whether pharmacologic agents that suppress PTH will prevent cortical and trabecular losses and post-transplant fractures. PMID:24511131

Depression is related to the alterations of the central serotonergic system and some antidepressants achieve their therapeutic effects through alteration of serotonin (5-HT) (re)uptake. Peripheral biochemical markers, platelet and serum 5-HT concentrations, platelet monoamine oxidase (MAO) activity, plasma levels of cortisol and prolactin (PRL), were investigated in patients with major depression before and after 4 weeks of treatment with paroxetine (an inhibitor of 5-HT uptake) or tianeptine (a stimulator of 5-HT uptake). Study was open, single center and included female depressed patients, 21 treated with tianeptine (37.5 mg/day) and 15 treated with paroxetine (20 mg/day), and 11 drug-free healthy women (controls). Before treatment, depressed patients as a group had significantly higher serum 5-HT and cortisol concentrations than healthy controls. There were no differences in the other biochemical markers. Response to antidepressant treatment was estimated according to the 50% fall in the initial scores of Hamilton Depression Rating Scale (HAMD) after 4 weeks of treatment. Good therapeutic response was observed in 47% and 45% patients treated with paroxetine and tianeptine, respectively. Paroxetine treatment induced significant decrease in platelet 5-HT concentrations in both responders and nonresponders, while no alterations in platelet 5-HT values were found in tianeptine-treated patients. There was a subgroup of depressed patients in paroxetine-treated group with high pretreatment platelet 5-HT concentration and later poor therapeutic response to paroxetine treatment. Serum 5-HT values, platelet MAO activity or plasma cortisol or PRL levels were unchanged after both treatments. The results suggest that pretreatment platelet 5-HT levels, but not other peripheral biochemical markers, might predict therapeutic outcome at least in paroxetine-treated patients. PMID:12502009

Ghrelin is an octanoylated peptide hormone that potently and rapidly increases food intake. The orexigenic action of ghrelin involves the hypothalamic arcuate nucleus (ARC), which is accessible to plasma ghrelin and expresses high levels of the ghrelin receptor. Local administration of ghrelin in a variety of other brain nuclei also increases food intake. It is currently unclear, however, whether these non-ARC ghrelin brain targets are impacted by physiological increases of plasma ghrelin. Thus, the present study aimed to clarify which ghrelin brain targets participate in the short-term orexigenic actions of ghrelin. First, c-Fos induction into mouse brains centrally or peripherally treated with ghrelin was analysed. It was confirmed that peripherally administered ghrelin dose-dependently increases food intake and mainly activates c-Fos in ARC neurones. By contrast, centrally administered ghrelin activates c-Fos in a larger number of brain nuclei. To determine which nuclei are directly accessible to ghrelin, mice were centrally or peripherally injected with a fluorescent ghrelin tracer. It was found that peripherally injected tracer mainly accesses the ARC, whereas centrally injected tracer reaches most brain areas known to express ghrelin receptors. Subsequently, the effects of ghrelin were tested in ARC-ablated mice and it was found that these mice failed to increase food intake in response to peripherally administered ghrelin but fully responded to centrally administered ghrelin. ARC-ablated mice showed patterns of ghrelin-induced c-Fos expression similar to those seen in control mice with the exception of the ARC, where no c-Fos was found. Thus, peripheral ghrelin mainly accesses the ARC, which is required for the orexigenic effects of the hormone. Central ghrelin accesses a variety of nuclei, which can mediate the orexigenic effects of the hormone, even in the absence of an intact ARC. PMID:24888783

Adenosine deaminase (ADA, E.C. 3.5.4.4) and purine nucleoside phosphorylase (PNP, E.C. 2.4.2.1) activities are essential for the normal development and function of T lymphocytes. A comparison of the specific activity of these two enzymes and of ecto-5'-nucleotidase (5'-N, E.C. 3.1.3.5) of human thymocytes with that of peripheral T lymphocytes of children and young adults shows that significant differences exist between the activities of ADA and 5'-N in thymocytes and peripheral T cells. ADA activity is six-fold higher in thymocytes than in peripheral T cells whereas 5'-N activity is approximately one-fourth lower in thymocytes than in T lymphocytes. PNP activity is two-fold higher in T cells. The apparent Km and Vmax values for the three enzymes in thymocytes and peripheral T lymphocytes have been determined. The observed differences in enzyme activity are probably not entirely due to differences in the affinity of the enzymes for their substrates. The enzyme activities of a thymoma removed from a patient with myasthenia gravis had intermediate enzyme levels for ADA and PNP, but 5'-N was similar to peripheral T cells. Exposure of thymocytes in short-term culture to the thymic hormones thymopoietin (the pentapeptide TP5), thymosin fraction V or serum thymic factor (FTS) had no significant stimulatory or inhibitory effect on the activities of the three enzymes under our experimental conditions. PMID:6287680

Grape seed proanthocyanidins (GSPs) possess a broad spectrum of pharmacological and therapeutic properties. The aim of this study was to examine the effect of GSPs on functional and morphological abnormalities in the peripheral nerves of rats with type 2 diabetes mellitus. Diabetic rats were induced by two injections of 25?mg streptozotocin/kg body weight and 8?weeks of a high-carbohydrate/high-fat diet. GSPs were then administrated to the rats for 16?weeks. Thermal and mechanical sensitivity thresholds and nerve conductive velocity were measured to evaluate peripheral nerve function. Light microscopy was used with special stains to observe the morphological changes in the central and peripheral nervous systems. Calcium (Ca(2+)) homeostasis and ATPase activities in the sciatic nerves were also determined. In diabetic rats receiving GSP treatment (especially at the 500?mg/kg dose), the abnormal peripheral nerve function and impaired nervous tissues (L4 to L5 spinal cord segments, L5 dorsal root ganglion, and sciatic nerves) were improved to a significant extent. Moreover, 500?mg/kg GSP treatment significantly reduced the concentration of free Ca(2+) and elevated Ca(2+)-ATPase activity in sciatic nerves. These results suggest that GSPs may prevent early functional and morphological abnormalities in the peripheral nerves of rats with type 2 diabetes mellitus. PMID:24343984

Objective: To study the relation between GCR expression and sensitivity of chemotherapy in patients with lymphoma. Methods: GCR sites in membrane of peripheral blood leucocyte and lymphocyte were determined by 3H-DEX, and the relation between the number of GCR site and sensitivity of chemotherapy was observed. Results: GCR expression of leucocyte and lymphocyte was basically at the same level, but patients with high GCR expression of lymphocyte were more sensitive to chemotherapy than those with high GCR expression of leucocyte, and chemotherapy did not affect the GCR expression. Conclusion: Determination of peripheral blood lymphocyte GCR is of greater value to prediction of curative effect of GC than that of leucocyte

It has been demonstrated previously that a short acute exposure to a specific extremely low frequency pulsed magnetic field (Cnp) can induce significant partly opioid-mediated analgesia in the land snail, Cepaea nemoralis. Here, this Cnp-induced analgesia is examined for the development of tolerance to daily repeated acute exposures of 15 or 30 min duration. Acute cross-tolerance to the delta opioid receptor directed agonist DPDPE, [D-Pen2, D-Pen5]enkephalin, was also found. Before (pre-exposure) and after (0, 15, 30 and 60 min) exposure to either a sham or Cnp magnetic field, snails were tested for an aversive reaction to a warmed surface (40 degrees C), and the latency time to the aversive reaction was recorded. Snails that were exposed to the Cnp showed a significant increase in the latency time (F1.55 = 2856.4; p < 0.001; Eta2 = 0.95), which may be interpreted as an induction of analgesia. During the daily (9 day) repeated acute exposures, the induction of analgesic response was significantly reduced, but not ablated. Altering the environmental conditions of the Cnp exposure restored a significant proportion of the partly developed tolerance, consistent with previous reports of environmental specificity in the development of opioid tolerance. These findings suggest that the partial development of tolerance to the opioid-mediated portion of Cnp-induced analgesia may be countered by altering the specific environmental Cnp exposure conditions. PMID:9493866

Full Text Available Acetylation level of chromatin histones is maintained by histone acetylases (HATs and deacetylases (HDACs and correlates with transcriptional activity of genes. Trichostatin A (TSA is HDAC inhibitor that causes various effects in cells, including immunomodulation. The CD4 antigen is a key coreceptor involved in activation of T helper cells. Using quantitative real-time PCR (RQ-PCR and flow cytometry techniques, we estimated CD4 transcript level and density of CD4 antigen on the surface of TSA-treated stimulated and unstimulated peripheral T cells. We observed a dose dependent decrease in CD4 mRNA level and antigen density on surface of TSA-treated stimulated T cells. However, we did not observe any significant TSA effect on CD4 mRNA and protein expression in unstimulated T cells. Our data suggest that TSA may induce biosynthesis of factors responsible for negative regulation of CD4 antigen expression in stimulated T cells. Our investigation may support previous observation that this drug has immunosuppresive effect on primary T cells and may be useful in treatment of certain autoimmune disorders.

Full Text Available Introduction: The peripheral facial paralysis (PFP results from the reduction or interruption of the axonal transport to the seventh cranial nerve resulting in complete or partial paralysis of the facial movements. The facial deformity and limitation of movements, besides affecting the aesthetics and functionality, can significantly interfere with interpersonal communication. Objective: Investigate the psychological contents and other social effects associated to PFP in adult subjects, performing a comparative analysis in three groups of subjects with PFP: at flaccid, recovery and sequel phases. Method: Quantitative and qualitative research. 16 adult subjects, from both sexes, aging between 43 and 88 years old, with PFP. Procedure: Open interviews with subjects. The material was recorded in audio and video, literally transcribed, systematized through categorical and statistical analysis. Results: The subjects bearing sequels presented higher statistical significance of psychological contents and social effects associated to PFP. Followed, respectively, by those that were on flaccid and recovery phases. The results suggest that the speech-language therapist, besides performing functional and aesthetical rehabilitation with the subject with PFP, needs to be aware of psychological and social aspects that may be involved, in order to evaluate and seek to reduce the degree of psychological distress and promote the social adjustment of these patients. Conclusion: The biopsychosocial approach to patients with PFP revealed a wide and significant range of subjective contents that warrant new studies that may contribute to the effectiveness of the speech-language clinical method to approach this medical condition.

The hemodynamic effect of L-propionylcarnitine (LPC) administered intravenously was evaluated in a double-blind, randomized, three-period crossover study in 12 men (aged sixty to seventy-five years) with Leriche-Fontaine stage II peripheral arterial disease of lower limbs. At baseline, maximum working capacity of each patient was determined by a standardized ergometric test. This test was repeated at 80% of each patient's maximum working capacity before and after intravenous administration of LPC. Each patient received three single doses of 300 mg, 600 mg, and 1200 mg of LPC with a two-day rest period between them. Hemodynamic variables measured by strain-gauge plethysmography were: peak blood flow, peak flow time, and halftime and total time of hyperemia both after exercise and after induction of ischemia (with an occlusion cuff). LPC administration significantly shortened the halftime as well as the total time of hyperemia after exercise and after ischemia. With the two highest doses, LPC shortened the peak flow time after exercise. The peak blood flow after exercise and after ischemia increased, but this increase did not reach statistical significance. The results obtained indicate that LPC improves circulatory reserve of the ischemic limb and has no effect on heart rate and arterial blood pressure. No adverse events were reported. The effect of LPC on the hyperemic response to stress, mainly on halftime of hyperemia, is possibly due to a drug-induced increase of adenosine triphosphate utilization by the ischemic tissues. PMID:7639417

Polycaprolactone (PCL)/Pluronic F127 nerve guide conduits (NGCs) with different surface pore structures (nano-porous inner surface vs. micro-porous inner surface) but similar physical and chemical properties were fabricated by rolling the opposite side of asymmetrically porous PCL/F127 membranes. The effect of the pore structure on peripheral nerve regeneration through the NGCs was investigated using a sciatic nerve defect model of rats. The nerve fibers and tissues were shown to have regenerated along the longitudinal direction through the NGC with a nano-porous inner surface (Nanopore NGC), while they grew toward the porous wall of the NGC with a micro-porous inner surface (Micropore NGC) and, thus, their growth was restricted when compared with the Nanopore NGC, as investigated by immunohistochemical evaluations (by fluorescence microscopy with anti-neurofilament staining and Hoechst staining for growth pattern of nerve fibers), histological evaluations (by light microscopy with Meyer's modified trichrome staining and Toluidine blue staining and transmission electron microscopy for the regeneration of axon and myelin sheath), and FluoroGold retrograde tracing (for reconnection between proximal and distal stumps). The effect of nerve growth factor (NGF) immobilized on the pore surfaces of the NGCs on nerve regeneration was not so significant when compared with NGCs not containing immobilized NGF. The NGC system with different surface pore structures but the same chemical/physical properties seems to be a good tool that is used for elucidating the surface pore effect of NGCs on nerve regeneration. PMID:22871377

cDNA microarray analysis showed the expression of peripheral-type benzodiazepine receptor (PBR) mRNA is slightly enhanced in the spinal cord of mice with spinal nerve injury (SNL) as compared with sham-operated mice. PBR transports cholesterol to the mitochondria, where cholesterol is converted to pregnenolone. Pregnenolone is then metabolized to progesterone, an activator of progesterone receptor, and further metabolized to produce allopregnanolone and 3alpha,21-dihydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THDOC), positive allosteric modulators and activators of the GABA(A) receptor. In the present study, we first tested whether the enhanced PBR expression is causally related to neuropathic pain, and we found that the PBR antagonist PK11195 is effective in reducing SNL-induced mechanical allodynia and thermal hyperalgesia. Next we tested whether the PK11195-induced antinociception is attributable to reduced neurosteroid synthesis, which may possibly lead to reduced activation of the progesterone receptor and/or GABA(A) receptor. We found that allopregnanolone and 3alpha,5alpha-THDOC are effective in reducing the anti-hyperalgesic effect of PK11195, suggesting a partial contribution of reduced GABA(A)-receptor activation to PK11195-induced antinociception. PMID:19403993

Gallium is commonly used in the semiconductor industry and medical field. Biologically, gallium is able to interrupt iron metabolism. Exposure to gallium has been shown to affect the human immune system. The purpose of this study was to investigate the in vitro biological effects of different gallium concentrations on cultured human peripheral blood mononuclear cells (PBMCs) in terms of cell growth, cytokine release, and apoptosis induction. In addition, the in vivo effects of gallium were analyzed by Wistar rat model. Our results revealed that low concentrations (1-10 ?g/ml) of gallium promoted cells to enter the S phase of cell cycle and enhanced cellular release of tumor necrosis factor-?, interleukin-1?, and interferon-?, both in vitro and in vivo. In contrast, high concentrations of gallium (50-100 ?g/ml) induced apoptosis. Furthermore, gallium-induced cytokine release and apoptosis could be inhibited by iron-saturated transferrin (Tf-Fe). These results suggest that the concentration-dependent effects of gallium on PBMCs are related to iron metabolism

Full Text Available Abstract Background The aim of this study is to investigate the effect of quercetin in alleviating the cytotoxic effects of Dimethoate in human peripheral blood lymphocytes. Methods Lymphocytes were divided into too groups. The first group, lymphocytes were incubated for 4 h at 37°C with different concentrations (0, 40, 60 and 100 mM of Dimethoate. The second group was preincubated with quercetin for 30 min and followed by Dim incubation for 4 h at 37°C. Results Following in vitro incubation, Dimethoate caused a significant increase in malondialdehyde levels, a significant decrease in thiol levels, as well as a significant increase in superoxide dismutase, and catalase activities in lymphocytes at different concentrations. Quercetin pretreated lymphocytes showed a significant protection against the cytotoxic effects inducted by Dimethoate on the studied parameters. Conclusion In conclusion, antioxidant quercetin could protect against Dimethoate-induced oxidative stress by decreasing lipid peroxidation, protein oxidation and increasing superoxide dismutase and catalase activities in human lymphocytes.

Narcotic analgesics produce pharmacological effects by interacting with specific opiate receptors. At least five major types of opiate receptors have been recognised. These include mu (morphine) and kappa (ethylketazocine) receptor types. Narcotic analgesics which interact with mu receptors produce locomotor and autonomic stimulation at doses that produce little or no analgesia. Therefore, use of these drugs as analgesics in equine medicine has not been very satisfactory. Theoretical considerations suggested that the role of kappa agonists in equine analgesia be investigated. Using a pure kappa agonist, U-50, 488H, good analgesia was produced in the horse with little or no locomotor stimulation or autonomic effects. These data suggest that kappa agonists may be superior analgesics for clinical use in the horse. On the other hand, the locomotor stimulant effects of mu agonist analgesics enable their use as illegal medications. Specifically, these agents produce a good running response, signs of central nervous stimulation and analgesia, all potentially useful effects in a racehorse. Regulatory control of most narcotic analgesics can be obtained by high performance thin layer chromatographic screening. However, effective screening for the fentanyls and small doses of etorphine can only be achieved by use of immunoassay. PMID:2563969

Full Text Available Objective To investigate the effect of hydrogen on streptozotocin (STZ-induced diabetic rat models with peripheral neuropathy and explore the possible mechanism. Methods Eighteen male Sprague-Dawley (SD rats were randomly divided into model group (N = 6, hydrogen-treated group (N = 6 and normal control group (N = 6. After fasting for 12 h, experimental diabetic rat models were established by intraperitoneal injection of STZ (65 mg/kg of single dose, while normal control group only received a same dose of citrate buffer. Diabetes was confirmed with a fasting plasma glucose more than 16.67 mmol/L 48 h after STZ injection. After diabetic models were established successively, hydrogen-rich saline (5 ml/kg was administered by intraperitoneal injection in hydrogen-treated group daily in 7th and 8th week after diabetes induction. Corresponding model and normal control groups received a same dose of normal saline. Changes of sciatic function and pain behavior in rats of different groups were measured to investigate the effect of hydrogen-rich saline. Proinflammatory cytokines, including tumor necrosis factor-? (TNF-? and interleukin-6 (IL-6, and nuclear factor-kappaB (NF-?B p65 expression were then determined to clarify the possible mechanism of hydrogen-mediated protection. Results 1 Compared with normal control group, body weight in model group decreased significantly, while plasma glucose levels increased significantly (P = 0.000, for all 8 weeks after STZ induction. Hydrogen did not show any effects on body weight and plasma glucose levels of treated rat models in comparison with model group (P = 0.256, 0.821. 2 Compared with normal control group, motor nerve conduction velocity (MNCV, heat pain threshold (HPT and mechanical withdrawal threshold (MWT decreased significantly in model group (P = 0.000, for all, but increased significantly in hydrogen-treated group when compared with model group in the 8th week (P = 0.000, for all. 3 Hydrogen also reduced the positively expressed cells of NF-?B p65 (P = 0.000 as well as levels of TNF-? and IL-6 (P = 0.000, for all. Conclusion Inflammation may participate and exaggerate painful diabetic neuropathy. Besides, hydrogen has the protective potential of ameliorating neuroinflammation and peripheral nerve injury by suppressing NF-?B pathway and its downstream inflammatory cytokines.

The pharmacological activities of the n -butanol alkaloids extracted from the stem bark of Hunteria zeylanica (Retz) Gardn. ex Thw. ( H. zeylanica ) and its major constituent, strictosidinic acid, on nociceptive response using writhing and hot plate tests, the antipyretic activity in yeast-induced fever, pentobarbital-induced sleep, and locomotor activity were examined in mice. Oral administration of H. zeylanica extract at 200 mg/kg significantly decreased the number of contortions and stretchings induced by acetic acid but not heat-induced pain. Strictosidinic acid (5-20 mg/kg, p.o.) also produced a similar effect but less pronounced than the extract. The antipyretic effect of strictosidinic acid (5-20 mg/kg, p.o.) was stronger than that of the extract (100-200 mg/kg, p.o.). The H. zeylanica extract dose-dependently (50-200 mg/kg, p.o.) prolonged the duration of pen-tobarbital-induced sleep but had no sign ificant effect on locomotor activity. No effect of strictosidinic acid was noted on both pentobarbital-induced sleep and locomotor activity. These results suggest that the H. zeylanica extract possesses peripheralanalgesic and mild antipyretic effects and its major constituent, strictosidinic acid, exerts a similar analgesiceffect with marked antipyretic activity. PMID:21214443

Full Text Available On the terminal part of the guinea-pig ileum GABA produces contraction whereas on the preterminal it produces an initial short-lasting contraction followed by a prolonged relaxation. The increasing range of concentrations of GABA produces a concentration-dependent decrease in contractions and an increase in contractions of the preterminal ileum. Both contractions and relaxations can be blocked by atropine, indicating the cholinergic nature of the responses. These effects are due to the action on GABAA receptors. Depending on the duration of the incubation period (3 and 60 sec GABA produced either potentiation or depression of the contractile effects of acetylcholine on the ileum. All the three neurotoxic insecticides (lindan malathion, permethrine affect the contractile effects of acetylcholine on the ileum. Lindan and permetrine antagonized the contractile effects of acetylcholine, whereas malathion produced a potentiation. Malathion significantly depressed the contractile effects of the electrical field stimulation of the ileum. This effect is probably realized through the local release of GABA. Both lindan and permethrine were found to decrease the duration of the barbiturate sleeping time, whereas malathion significantly prolonged its duration. The action of lindan and permethrine is presumably realized by blocking or interfering with the function of GABAA receptors. Malathion is an anticholinesterase, thus producing an accumulation of acetylcholine at the critical sites, consequently producing a prolongation of the barbiturate sleeping time. In conclusion, neurotoxic insecticides (lindan, permethrine, malathion affect both central and peripheral GABA-ergic systems. They can produce either depression or stimulation of these systems. They also highly significantly modulate the activity of the cholinergic system in the isolated guinea-pig ileum.

Opioids constitute the basis for pharmacological treatment of moderate to severe pain in cancer pain and non-cancer pain patients. Their action is mediated by the activation of opioid receptors, which integrates the pain modulation system with other effects in the central nervous system including cognition resulting in complex interactions between pain, opioids and cognition. The literature on this complexity is sparse and information regarding the cognitive effects of opioids in chronic pain patients is substantially lacking. Two previous systematic reviews on cancer pain and non-cancer pain patients only using controlled studies were updated. Fourteen controlled studies on the cognitive effects of opioids in chronic non-cancer pain patients and eleven controlled studies in cancer pain patients were included and analyzed. Opioid treatment involved slightly opposite outcomes in the two patient groups: no effects or worsening of cognitive function in cancer pain patients and no effect or improvements in the chronic non-cancer pain patients, however, due to methodological limitations and a huge variety of designs definite conclusions are difficult to draw from the studies. In studies of higher quality of evidence opioid induced deficits in cognitive functioning were associated with dose increase and the use of supplemental doses of opioids in cancer patients. Future perspectives should comprise the conduction of high quality randomized controlled trials (RCTs) involving relevant control groups and validated neuropsychological assessments tools before and after opioid treatment in order to further explore the complex interaction between pain, opioids and cognition.

In 60 women with breast carcinoma treated by radical mastectomy followed by X-ray treatment the effect of radiotherapy on the absolute values of different subpopulations of lymphoid cells in the peripheral blood was investigated. In evaluating the effect of radiotherapy on the system of lymphoid cells the technique of rosette tests was used, with the rosette test E applied for determination of lymphocytes T, the EAC test used for determining lymphocytes B, and the Esub(act) test for Tsub(active) lymphocytes. On the basis of the obtained results it is concluded that postoperative radiotherapy in breast carcinoma causes lymphopenia T due, in the first place, to a fall in the number of cells forming active rosettes E. The participation of disturbances in the subpopulation of lymphocytes B is less evident. Disturbances in all lymphoid cells tested developed already at the time of radiotherapy reaching a maximum value immediately after its end and persisting for at least 12 months. The degree of postradiation damage to the lymphocyte system increases with increasing dose of radiation applied and when the thymus is included into the irradiated area. (author)

Full Text Available Centella asiatica (CA is a medicinal herb which has been valued in ayurvedicmedicine for its different activities. In the present studies, CA methanolic extract wasprepared by Soxhlet extraction and then evaluated for the cytotoxicity and genotoxicity incultured human peripheral blood lymphocytes. Mitotic Index (MI Cell ProliferationKinetics (CPK and Sister-chromatid exchanges (SCE were scored to measure thecytotoxic and genotoxic effects of the CA extract in cultures set up from the three differenthealthy donors. The treatment of the cell culture was done employing two different CAmethanolic extract concentrations (500 & 1000 ?g/ml and the control (did not receive anyadditive. Our present studies revealed that the MI, CPK and SCES for control are 4.28,0.49 and 6.08 respectively where as the CA extracts has the MI, CPK and SCES for500?g/ml are 4.07, 0.47 and 5.84 respectively and for 1000 ?g/ml are 3.96, 0.46 and 5.52respectively. From the results, we can conclude that the MI and frequency of SCES of CAmethanolic extracts are almost similar to that of control which indicates that the CA plantextracts has no significant cytotoxicity and genotoxicity effects in cultured humanperipheral blood lymphocytes.

Immunotherapy has raised the attention of many scientists because it hold promise to be an attractive therapeutic strategy to treat a number of disorders. In this study, the immunomodulatory effects of low titers of Newcastle disease virus (NDV) AF2240 on human peripheral blood mononuclear cells (PBMC) were analyzed. We evaluated cytokine secretion and PBMC activation by cell proliferation assay, immunophenotyping and enzyme linked immunosorbent assay. The proliferation of the human PBMC was measured to be 28.5% and 36.5% upon treatment with 8 hemaglutinin unit (HAU) and 2 HAU of NDV respectively. Interestingly, the percentage of cells with activating markers CD16 and CD56 were increased significantly. Furthermore, the intracellular perforin and granzyme levels were also increased upon virus infection. Human PBMC treated with NDV titer 8 HAU was found to stimulate the highest level of cytokine production including interferon-?, interleukin-2 and interleukin-12. The release of these proteins contributes to the antitumor effect of PBMC against MCF-7 breast cancer cells. Based on the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay, activated human PBMC showed high cytolytic efficiency towards human breast tumor cells. In summary, NDV was able to stimulate PBMC proliferation, cytokine secretion and cytolytic activity. PMID:25317070

Beagle dogs were exposed by inhalation to 144Ce in fused aluminosilicate particles, a relatively insoluble, inert carrier material. The radioactive particles deposited in the deep lung resulted in chronic irradiation of the pulmonary and adjacent thoracic tissues. Dogs exposed to high levels of 144Ce in fused aluminosilicate particles received more than 25,000 rad to lung by 3 yr after exposure. They developed a severe and persistent lymphopenia, and their remaining peripheral lymphocytes showed a decreased ability to respond to plant mitogens in vitro. The lymphopenia and the functional defect in the remaining lymphocytes suggested that an immunologic suppression existed in these dogs. Many lymphocytes were being killed in vivo by the radiation but another population was present that was viable in vivo but died when placed in vitro, accounting for at least part of the reduction in response to plant mitogens. No plasma factor was found that could account for the reduced lymphocyte transformation. The 144Ce-exposed dogs developed a high incidence of primary pulmonary hemangiosarcomas between 1 and 5 yr after exposure. This suggests that carcinogenesis after intrapulmonary deposition of radionuclides may result from a combination of the direct carcinogenic effect and the immunosuppressive effect of the irradiation

Sulphated polysaccharides from marine algae are widely used in biotechnological and pharmaceutical areas. In this study, we evaluated the effects of sulphated polysaccharides from the green marine alga Caulerpa mexicana (Cm-SPs) in nociceptive and inflammatory models in rodents. Cm-SPs (10 or 20 mg/kg), administered i.v. in Swiss mice, significantly reduced nociceptive responses, as measured by the number of writhes in response to acetic acid. Cm-SPs (10 or 20 mg/kg) also reduced second-phase responses in the formalin test, but did not exhibit a significant antinociceptive effect in the hot plate test, suggesting that its antinociceptive action occurs through a peripheral mechanism. Cm-SPs (5, 10 or 20 mg/kg), administered s.c. in wistar rats 1 hr before carrageenan, dextran, histamine or serotonin, were tested in paw oedema models. Cm-SPs (10 or 20 mg/kg) reduced carrageenan-induced paw oedema and myeloperoxidase activity in the paw. In addition, Cm-SPs (20 mg/kg) inhibited dextran- or histamine-induced paw oedema, but not serotonin-induced oedema, suggesting that histamine is the major target of Cm-SPs anti-oedematogenic activity. Finally, Cm-SPs (20 mg/kg) administered in mice did not show significant signs of toxicity. In conclusion, Cm-SPs appear to be promising natural modulatory agents for pain and inflammatory conditions. PMID:24674382

Infiltration of circulatory inflammatory cells is a common histopathological finding in target organs following cadmium administration, but there is paucity of data concerning their activity. In this study, the effects of sublethal (1 mg/kg) cadmium on peripheral blood polymorphonuclear (PMN) cells were examined 48 h following administration in rats, when tissue (liver and lung) infiltration of these cells was observed. Cadmium administration resulted in systemic inflammatory cytokine and acute phase response with an increase in circulatory neutrophil numbers and cells that express CD11b molecules. Rise in basic aspects of oxidative activity including intracellular myeloperoxidase (MPO), reactive oxygen (nitroblue tetrazolium/NBT cytochemical assay) and nitrogen (Griess assay) species production was observed in PMNs from cadmium-administered rats. A decrease in levels of mRNA for IL-1?, TNF-? and IL-6 was noted, but production of these cytokines was affected differentially. Described effects of cadmium on PMNs add further to the understanding of inflammatory potential of this environmental contaminant. PMID:24361699

Objectives: This study investigates the in vitro effect of the antioxidant drug, N-acetyl-L-cysteine (NAC), on cytokine production by peripheral blood mononuclear cells (PBMC). Methods: PBMC were isolated by Ficoll-Hypaque, and stimulated with anti-CD3 antibodies, phytohaemagglutinin (PHA), lipopolysaccharide (LPS) for 24 hours in the presence or absence of 5 mM NAC. The cytokines produced were measured by enzyme-linked immunosorbent assay (ELISA). Results: Treatment with NAC significantly up-regulates the secretion of IL-1?, IL-5 (interleukin) and IFN-? (interferon) and down regulates IL-10 production, after anti-CD3 or PHA (p<0.05), but not after LPS stimulation. NAC also significantly increased total IL-12 secretion after anti-CD3 (but not PHA or LPS) stimulation and IL-12p40 after anti-CD3, PHA, and LPS stimulation (p <0.05). Conclusion: These results indicate that NAC up-regulated the production of pro-inflammatory cytokines, and down regulated anti-inflammatory cytokine production by PBMC, in a process which may be associated with increased levels of glutathione (GSH). Further work is required to determine whether this increase or decrease in cytokine production is due to direct effect of NAC. PMID:21509278

Exogenous and endogenous damage to DNA is constantly challenging the stability of our genome. This DNA damage increase the frequency of errors in DNA replication, thus causing point mutations or chromosomal rearrangements and has been implicated in aging, cancer, and neurodegenerative diseases. Therefore, efficient DNA repair is vital for the maintenance of genome stability. The general notion has been that DNA repair capacity decreases with age although there are conflicting results. Here, we focused on potential age-associated changes in DNA damage response and the capacities of repairing DNA single-strand breaks (SSBs) and double-strand breaks (DSBs) in human peripheral blood mononuclear cells (PBMCs). Of these lesions, DSBs are the least frequent but the most dangerous for cells. We have measured the level of endogenous SSBs, SSB repair capacity, ?-H2AX response, and DSB repair capacity in a study population consisting of 216 individuals from a population-based sample of twins aged 40-77 years. Age in this range did not seem to have any effect on the SSB parameters. However, ?-H2AX response and DSB repair capacity decreased with increasing age, although the associations did not reach statistical significance after adjustment for batch effect across multiple experiments. No gender differences were observed for any of the parameters analyzed. Our findings suggest that in PBMCs, the repair of SSBs is maintained until old age, whereas the response to and the repair of DSBs decrease

Pain models in animals have shown low predictivity for analgesic efficacy in humans, and clinical studies are often very confounded, blurring the evaluation. Human experimental pain models may therefore help to evaluate mechanisms and effect of analgesics and bridge findings from basic studies to the clinic. The present review outlines the concept and limitations of human experimental pain models and addresses analgesic efficacy in healthy volunteers and patients. Experimental models to evoke pain and hyperalgesia are available for most tissues. In healthy volunteers, the effect of acetaminophen is difficult to detect unless neurophysiological methods are used, whereas the effect of nonsteroidal anti-inflammatory drugs could be detected in most models. Anticonvulsants and antidepressants are sensitive in several models, particularly in models inducing hyperalgesia. For opioids, tonic pain with high intensity is attenuated more than short-lasting pain and nonpainful sensations. Fewer studies were performed in patients. In general, the sensitivity to analgesics is better in patients than in healthy volunteers, but the lower number of studies may bias the results. Experimental models have variable reliability, and validity shall be interpreted with caution. Models including deep, tonic pain and hyperalgesia are better to predict the effects of analgesics. Assessment with neurophysiologic methods and imaging is valuable as a supplement to psychophysical methods and can increase sensitivity. The models need to be designed with careful consideration of pharmacological mechanisms and pharmacokinetics of analgesics. Knowledge obtained from this review can help design experimental pain studies for new compounds entering phase I and II clinical trials.

The aerial part of Salvia wiedemannii Boiss. (Lamiaceae) has been used for treatment of peptic ulcers and relieving pain in Turkish folk medicine. To evaluate the analgesiceffect of S. wiedemannii, tail flick and acetic acid-induced writhing tests were used in mice. The chloroform extract (500 mg/kg, i.p.) obtained from S. wiedemannii showed significant analgesic activity on tail flick assay, while water, ethanol and butanol extracts of the plant had no activity on the same test. Chloroform ...

Objectives: To evaluate the knowledge of nurses about the analgesics they administer in our hospital. Methodology: A total of 102 nurses completed the questionnaire which included 20 multiple choice questions based on the dosage forms, mechanism of action, route of administration, adverse effects of the commonly administered analgesics, the nurses’ educational qualifications and their working experience. Frequency, percentage, mean, Kruskal Wallis test and Mann Whitneys test were used to an...

The crude aqueous extract of the fruits of Caesalpinia ferrea Mart. (Leguminosae) has been investigated for possible anti-inflammatory and analgesic properties. The carrageenan induced rat hind paw edema was significantly inhibited (P < 0.05) by oral administration of 300 mg/kg of this extract. A centrally mediated analgesiceffect was not observed, however, there was a dose dependent reduction in the number of total writhes induced by acetic acid. PMID:8887026

Full Text Available The early facilitatory effect of a peripheral spatially visual prime stimulus described in the literature for simple reaction time tasks has been usually smaller than that described for complex (go/no-go, choice reaction time tasks. In the present study we investigated the reason for this difference. In a first and a second experiment we tested the participants in both a simple task and a go/no-go task, half of them beginning with one of these tasks and half with the other one. We observed that the prime stimulus had an early effect, inhibitory for the simple task and facilitatory for the go/no-go task, when the task was performed first. No early effect appeared when the task was performed second. In a third and a fourth experiment the participants were, respectively, tested in the simple task and in the go/no-go task for four sessions (the prime stimulus was presented in the second, third and fourth sessions. The early effects of the prime stimulus did not change across the sessions, suggesting that a habituatory process was not the cause for the disappearance of these effects in the first two experiments. Our findings are compatible with the idea that different attentional strategies are adopted in simple and complex reaction time tasks. In the former tasks the gain of automatic attention mechanisms may be adjusted to a low level and in the latter tasks, to a high level. The attentional influence of the prime stimulus may be antagonized by another influence, possibly a masking one.

Full Text Available SciELO Brazil | Language: English Abstract in english The early facilitatory effect of a peripheral spatially visual prime stimulus described in the literature for simple reaction time tasks has been usually smaller than that described for complex (go/no-go, choice) reaction time tasks. In the present study we investigated the reason for this differenc [...] e. In a first and a second experiment we tested the participants in both a simple task and a go/no-go task, half of them beginning with one of these tasks and half with the other one. We observed that the prime stimulus had an early effect, inhibitory for the simple task and facilitatory for the go/no-go task, when the task was performed first. No early effect appeared when the task was performed second. In a third and a fourth experiment the participants were, respectively, tested in the simple task and in the go/no-go task for four sessions (the prime stimulus was presented in the second, third and fourth sessions). The early effects of the prime stimulus did not change across the sessions, suggesting that a habituatory process was not the cause for the disappearance of these effects in the first two experiments. Our findings are compatible with the idea that different attentional strategies are adopted in simple and complex reaction time tasks. In the former tasks the gain of automatic attention mechanisms may be adjusted to a low level and in the latter tasks, to a high level. The attentional influence of the prime stimulus may be antagonized by another influence, possibly a masking one.

Dogs that have inhaled relatively insoluble forms of either alpha- or beta-emitting radionuclides manifest a peripheral lymphopenia, the development and course of which is both total dose and dose-rate dependent. The remaining peripheral lymphocytes in dogs exposed to longer lived beta-emitting radionuclides show depressed response to plant mitogens in vitro. This experiment was designed to evaluate the effect of dose rate on peripheral lymphocyte function by exposing dogs to aerosols of radionuclides with varied effective half-lives in the lungs; 90Y (2.6 days), 144Ce (170 days), and 90Sr (650 days). Three groups of four adult Beagle dogs each were exposed by inhalation to 90Y, 144Ce, or 90Sr in fused clay particles. Two controls were matched with each group. Hematologic parameters and lymphocyte function as measured by the ability of lymphocytes to respond to plant mitogen stimulation were evaluated on a weekly or biweekly basis through 8 weeks post-exposure and monthly thereafter. The 90Y-exposed dogs showed a marked lymphopenia within one week with a return to control levels by 20 weeks post-exposure. The remaining peripheral lymphocytes, however, showed no functional changes in these dogs. Animals exposed to 144Ce or 90Sr in fused clay developed a progressive and persistent lymphopenia and showed functional depression of the remaining lymphocytes as well. The relationships between dose pattern, lymphopenia, and lymphocyte function depression are discussed. (U.S.)

Ocular following responses induced by brief movements of the visual scene were examined in monkeys for their dependence on disparity in the peripheral field. A random dot pattern was projected onto a tangent screen and partitioned into central and peripheral regions. Test stimuli were velocity steps applied in the central region, while stimuli in the periphery were stationary. The visual images in the central region were seen always in the plane of the screen, while stimuli in the periphery could be seen in front, behind, or in the plane of the screen (achieved by a system of polarizing filters). Initial ocular following responses were larger when the peripheral stimuli were presented with an uncrossed disparity than without disparity. On the other hand, responses were smaller when the peripheral stimuli were presented with crossed disparity (consistent with the idea that ocular following responses are dependent on the perceived viewing distance. PMID:7918233

There were investigated changes in the peripheral blood of rabbits under prolonged exposure to vibration (5, 10, 20, 30 days). In a separate series of experiments, the nature of changes in the peripheral blood was investigated under the combined action of vibration and stevia leaves. Contained in stevia biologically active substances were found to accelerate metabolism in bone marrow stem cells, promote the compensatory ability of the organism, thereby providing the resistance of the body to the vibration factor. PMID:25306709

From counts made 10 and 14 days after irradiation, it appeared that 200 mg/kg of AET efficiently prevented the reduction of erythrocytes in peripheral mouse blood after 760 R gamma irradiation. However, MPG did not protect the depression in RBC level in peripheral blood after gamma exposure. Moreover, when administered in combination with 200 mg/kg AET, it hindered partially the protection rendered by AET. (U.K.)

Full Text Available The aim of this work was to investigate whether acamprosate modifies the expression of the enzyme responsible for neuronal NO synthesis (nNOS in the nucleus accumbens (NAc of mice chronically treated with morphine and during the abstinence syndrome induced by naloxone. The enzyme was monitored by the NADPH diaphorase method. The number of cells stained for NADPH diaphorase in the NAc of mice was counted in 40 ?m thick coronal brain slices at 40X. The intensity of the histochemical reaction of stained cells from naive morphine plus saline and morphine plus acamprosate treated mice was analyzed by Image Pro Plus 4.5.1. Morphine administered in a slow release preparation increased the stain intensity of the positive neurons. The increase in the NADPH staining persisted after naloxone was given to mice chronically treated with morphine. Acamprosate antagonized the effects induced by chronic morphine treatment in the NAc of mice. These results indicate that up-regulation of nNOS in the NAc is a consequence of the sustained effects of morphine stimulation, which, in turn, may result from an increased in glutamate release during the abstinence syndrome.

Do spatial attention and object attention modulate visual processing in similar ways? Previously we have found a dissociation between these two forms of attention on ERP measures of sensory processing under conditions of peripheral cueing, with spatial attention effects associated with changes over anterior scalp regions and object attention